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image of Phytomolecules from Herbs: Possible Effective Way for the Treatment of Liver Cancer

Abstract

Liver cancer is the sixth most commonly diagnosed cancer globally, accounting for approximately 50% of all diagnosed cases and associated mortalities. The principal therapeutic strategies for liver cancer presently include surgical intervention, radiotherapy, and laser ablation therapies. All these therapies are effective for liver cancer at an early stage and have limited efficacy for advanced-stage cancer due to severe side effects and drug resistance. The plant-derived natural product, . phyto-constituents, has been evaluated as a potential anticancer drug due to low side effects and antitumor efficacy. Many studies support the effectiveness of active phytoconstituents found in various plants such as garlic, turmeric, tomatoes, grapes, pomegranates, plums, black currants, French beans, cruciferous vegetables, ginger, and asparagus. These plants are reported to have very diversified groups of compounds such as alkaloids, flavonoids, phenolics, terpenoids, coumarin, ., attributed to medicinal values and biological activities such as antiviral, antioxidant, anti-inflammatory, anticancer, . These plants provide important nutrients and help to maintain health, thereby reducing the risk of disease. Almost 50 drugs are directly or indirectly derived from natural sources because of minimum side effects and diversified chemical compounds. In this review, the anticancer properties of edible plants-derived phytomolecules, such as glycyrrhizin, triptolide, celastrol, berberine hydrochloride, curcumin, stilbenes, ., against Hepatocellular Carcinoma (HCC) are discussed in detail. Phytomolecules discussed in this review for HCC could be promising leads or drugs as anticancer agents from economical and easily available plant sources.

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2025-04-21
2025-09-13
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References

  1. Balogh J. Victor D. III Asham E.H. Burroughs S.G. Boktour M. Saharia A. Li X. Ghobrial M. Monsour H. Jr Hepatocellular carcinoma: A review. J. Hepatocell. Carcinoma 2016 3 41 53 10.2147/JHC.S61146 27785449
    [Google Scholar]
  2. Marquardt J.U. Andersen J.B. Thorgeirsson S.S. Functional and genetic deconstruction of the cellular origin in liver cancer. Nat. Rev. Cancer 2015 15 11 653 667 10.1038/nrc4017 26493646
    [Google Scholar]
  3. Torre L.A. Bray F. Siegel R.L. Ferlay J. Lortet-Tieulent J. Jemal A. Global cancer statistics, 2012. CA Cancer J. Clin. 2015 65 2 87 108 10.3322/caac.21262 25651787
    [Google Scholar]
  4. de Jong M.C. Nathan H. Sotiropoulos G.C. Paul A. Alexandrescu S. Marques H. Pulitano C. Barroso E. Clary B.M. Aldrighetti L. Ferrone C.R. Zhu A.X. Bauer T.W. Walters D.M. Gamblin T.C. Nguyen K.T. Turley R. Popescu I. Hubert C. Meyer S. Schulick R.D. Choti M.A. Gigot J.F. Mentha G. Pawlik T.M. Intrahepatic cholangiocarcinoma: An international multi-institutional analysis of prognostic factors and lymph node assessment. J. Clin. Oncol. 2011 29 23 3140 3145 10.1200/JCO.2011.35.6519 21730269
    [Google Scholar]
  5. Chatterjee R. Mitra A. An overview of effective therapies and recent advances in biomarkers for chronic liver diseases and associated liver cancer. Int. Immunopharmacol. 2015 24 2 335 345 10.1016/j.intimp.2014.12.024 25560752
    [Google Scholar]
  6. Wang H. Lu Z. Zhao X. Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer. J. Hematol. Oncol. 2019 12 1 133 10.1186/s13045‑019‑0806‑6 30606227
    [Google Scholar]
  7. Darvesh A.S. Bishayee A. Chemopreventive and therapeutic potential of tea polyphenols in hepatocellular cancer. Nutr. Cancer 2013 65 3 329 344 10.1080/01635581.2013.767367 23530632
    [Google Scholar]
  8. Ha H.L. Shin H.J. Feitelson M.A. Yu D.Y. Oxidative stress and antioxidants in hepatic pathogenesis. World J. Gastroenterol. 2010 16 48 6035 6043 10.3748/wjg.v16.i48.6035 21182217
    [Google Scholar]
  9. Klaunig J.E. Kamendulis L.M. The role of oxidative stress in carcinogenesis. Annu. Rev. Pharmacol. Toxicol. 2004 44 1 239 267 10.1146/annurev.pharmtox.44.101802.121851 14744246
    [Google Scholar]
  10. Pang R. Tse E. Poon R.T.P. Molecular pathways in hepatocellular carcinoma. Cancer Lett. 2006 240 2 157 169 10.1016/j.canlet.2005.08.031 16239065
    [Google Scholar]
  11. Wong C.M. Ng I.O.L. Molecular pathogenesis of hepatocellular carcinoma. Liver Int. 2008 28 2 160 174 10.1111/j.1478‑3231.2007.01637.x 18069974
    [Google Scholar]
  12. Frau M. Biasi F. Feo F. Pascale R.M. Prognostic markers and putative therapeutic targets for hepatocellular carcinoma. Mol. Aspects Med. 2010 31 2 179 193 10.1016/j.mam.2010.02.007 20176048
    [Google Scholar]
  13. Singal A.G. El-Serag H.B. Hepatocellular carcinoma from epidemiology to prevention: Translating knowledge into practice. Clin. Gastroenterol. Hepatol. 2015 13 12 2140 2151 10.1016/j.cgh.2015.08.014 26284591
    [Google Scholar]
  14. Gomes M.A. Priolli D.G. Tralhão J.G. Botelho M.F. Hepatocellular carcinoma: Epidemiology, biology, diagnosis, and therapies. Rev. Assoc. Med. Bras. 2013 59 5 514 524 10.1016/j.ramb.2013.03.005 24041910
    [Google Scholar]
  15. Finn R.S. Emerging targeted strategies in advanced hepatocellular carcinoma. Semin. Liver Dis. 2013 33 S 01 S11 S19 10.1055/s‑0033‑1333632
    [Google Scholar]
  16. Okuda K. Hepatocellular carcinoma. J. Hepatol. 2000 32 1 Suppl. 225 237 10.1016/S0168‑8278(00)80428‑6 10728807
    [Google Scholar]
  17. Takayasu K. Muramatsu Y. Moriyama N. Hasegawa H. Makuuchi M. Okazaki N. Hirohashi S. Tsugane S. Clinical and radiologic assessments of the results of hepatectomy for small hepatocellular carcinoma and therapeutic arterial embolization for postoperative recurrence. Cancer 1989 64 9 1848 1852 10.1002/1097‑0142(19891101)64:9<1848::AID‑CNCR2820640916>3.0.CO;2‑5 2477137
    [Google Scholar]
  18. Sato M. Watanabe Y. Ueda S. Iseki S. Abe Y. Sato N. Kimura S. Okubo K. Onji M. Microwave coagulation therapy for hepatocellular carcinoma. Gastroenterology 1996 110 5 1507 1514 10.1053/gast.1996.v110.pm8613057 8613057
    [Google Scholar]
  19. Llovet J.M. Burroughs A. Bruix J. Hepatocellular carcinoma. Lancet 2003 362 9399 1907 1917 10.1016/S0140‑6736(03)14964‑1 14667750
    [Google Scholar]
  20. Dai X.Z. Yin H.T. Sun L.F. Hu X. Zhou C. Zhou Y. Zhang W. Huang X.E. Li X.C. Potential therapeutic efficacy of curcumin in liver cancer. Asian Pac. J. Cancer Prev. 2013 14 6 3855 3859 10.7314/APJCP.2013.14.6.3855 23886196
    [Google Scholar]
  21. Xia J. Gao J.J. Inagaki Y. Kokudo N. Nakata M. Tang W. Flavonoids as potential anti-hepatocellular carcinoma agents: Recent approaches using HepG2 cell line. Drug Discov. Ther. 2013 7 1 1 8 10.5582/ddt.2013.v7.1.1 23524937
    [Google Scholar]
  22. Mokdad A.A. Lopez A.D. Shahraz S. Lozano R. Mokdad A.H. Stanaway J. Murray C.J.L. Naghavi M. Liver cirrhosis mortality in 187 countries between 1980 and 2010: A systematic analysis. BMC Med. 2014 12 1 145 10.1186/s12916‑014‑0145‑y 25242656
    [Google Scholar]
  23. Rehm J. Mathers C. Popova S. Thavorncharoensap M. Teerawattananon Y. Patra J. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet 2009 373 9682 2223 2233 10.1016/S0140‑6736(09)60746‑7 19560604
    [Google Scholar]
  24. World Health Organization Department of Mental Health, Substance Abuse. Global status report on alcohol 2004. World Health Organization 2004
    [Google Scholar]
  25. World Health Organization Global status report on alcohol and health 2018. World Health Organization 2018
    [Google Scholar]
  26. Stein E. Cruz-Lemini M. Altamirano J. Ndugga N. Couper D. Abraldes J.G. Bataller R. Heavy daily alcohol intake at the population level predicts the weight of alcohol in cirrhosis burden worldwide. J. Hepatol. 2016 65 5 998 1005 10.1016/j.jhep.2016.06.018 27392424
    [Google Scholar]
  27. Petroni M.L. Brodosi L. Bugianesi E. Marchesini G. Management of non-alcoholic fatty liver disease. BMJ 2021 372 m4747 10.1136/bmj.m4747 33461969
    [Google Scholar]
  28. Flegal K.M. Carroll M.D. Kit B.K. Ogden C.L. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA 2012 307 5 491 497 10.1001/jama.2012.39 22253363
    [Google Scholar]
  29. Rinella M. Charlton M. The globalization of nonalcoholic fatty liver disease: Prevalence and impact on world health. Hepatology 2016 64 1 19 22 10.1002/hep.28524 26926530
    [Google Scholar]
  30. Murray C.J.L. Vos T. Lozano R. Naghavi M. Flaxman A.D. Michaud C. Ezzati M. Shibuya K. Salomon J.A. Abdalla S. Aboyans V. Abraham J. Ackerman I. Aggarwal R. Ahn S.Y. Ali M.K. AlMazroa M.A. Alvarado M. Anderson H.R. Anderson L.M. Andrews K.G. Atkinson C. Baddour L.M. Bahalim A.N. Barker-Collo S. Barrero L.H. Bartels D.H. Basáñez M-G. Baxter A. Bell M.L. Benjamin E.J. Bennett D. Bernabé E. Bhalla K. Bhandari B. Bikbov B. Abdulhak A.B. Birbeck G. Black J.A. Blencowe H. Blore J.D. Blyth F. Bolliger I. Bonaventure A. Boufous S. Bourne R. Boussinesq M. Braithwaite T. Brayne C. Bridgett L. Brooker S. Brooks P. Brugha T.S. Bryan-Hancock C. Bucello C. Buchbinder R. Buckle G. Budke C.M. Burch M. Burney P. Burstein R. Calabria B. Campbell B. Canter C.E. Carabin H. Carapetis J. Carmona L. Cella C. Charlson F. Chen H. Cheng A.T-A. Chou D. Chugh S.S. Coffeng L.E. Colan S.D. Colquhoun S. Colson K.E. Condon J. Connor M.D. Cooper L.T. Corriere M. Cortinovis M. de Vaccaro K.C. Couser W. Cowie B.C. Criqui M.H. Cross M. Dabhadkar K.C. Dahiya M. Dahodwala N. Damsere-Derry J. Danaei G. Davis A. Leo D.D. Degenhardt L. Dellavalle R. Delossantos A. Denenberg J. Derrett S. Des Jarlais D.C. Dharmaratne S.D. Dherani M. Diaz-Torne C. Dolk H. Dorsey E.R. Driscoll T. Duber H. Ebel B. Edmond K. Elbaz A. Ali S.E. Erskine H. Erwin P.J. Espindola P. Ewoigbokhan S.E. Farzadfar F. Feigin V. Felson D.T. Ferrari A. Ferri C.P. Fèvre E.M. Finucane M.M. Flaxman S. Flood L. Foreman K. Forouzanfar M.H. Fowkes F.G.R. Fransen M. Freeman M.K. Gabbe B.J. Gabriel S.E. Gakidou E. Ganatra H.A. Garcia B. Gaspari F. Gillum R.F. Gmel G. Gonzalez-Medina D. Gosselin R. Grainger R. Grant B. Groeger J. Guillemin F. Gunnell D. Gupta R. Haagsma J. Hagan H. Halasa Y.A. Hall W. Haring D. Haro J.M. Harrison J.E. Havmoeller R. Hay R.J. Higashi H. Hill C. Hoen B. Hoffman H. Hotez P.J. Hoy D. Huang J.J. Ibeanusi S.E. Jacobsen K.H. James S.L. Jarvis D. Jasrasaria R. Jayaraman S. Johns N. Jonas J.B. Karthikeyan G. Kassebaum N. Kawakami N. Keren A. Khoo J-P. King C.H. Knowlton L.M. Kobusingye O. Koranteng A. Krishnamurthi R. Laden F. Lalloo R. Laslett L.L. Lathlean T. Leasher J.L. Lee Y.Y. Leigh J. Levinson D. Lim S.S. Limb E. Lin J.K. Lipnick M. Lipshultz S.E. Liu W. Loane M. Ohno S.L. Lyons R. Mabweijano J. MacIntyre M.F. Malekzadeh R. Mallinger L. Manivannan S. Marcenes W. March L. Margolis D.J. Marks G.B. Marks R. Matsumori A. Matzopoulos R. Mayosi B.M. McAnulty J.H. McDermott M.M. McGill N. McGrath J. Medina-Mora M.E. Meltzer M. Memish Z.A. Mensah G.A. Merriman T.R. Meyer A-C. Miglioli V. Miller M. Miller T.R. Mitchell P.B. Mock C. Mocumbi A.O. Moffitt T.E. Mokdad A.A. Monasta L. Montico M. Moradi-Lakeh M. Moran A. Morawska L. Mori R. Murdoch M.E. Mwaniki M.K. Naidoo K. Nair M.N. Naldi L. Narayan K.M.V. Nelson P.K. Nelson R.G. Nevitt M.C. Newton C.R. Nolte S. Norman P. Norman R. O’Donnell M. O’Hanlon S. Olives C. Omer S.B. Ortblad K. Osborne R. Ozgediz D. Page A. Pahari B. Pandian J.D. Rivero A.P. Patten S.B. Pearce N. Padilla R.P. Perez-Ruiz F. Perico N. Pesudovs K. Phillips D. Phillips M.R. Pierce K. Pion S. Polanczyk G.V. Polinder S. Pope C.A. III Popova S. Porrini E. Pourmalek F. Prince M. Pullan R.L. Ramaiah K.D. Ranganathan D. Razavi H. Regan M. Rehm J.T. Rein D.B. Remuzzi G. Richardson K. Rivara F.P. Roberts T. Robinson C. De Leòn F.R. Ronfani L. Room R. Rosenfeld L.C. Rushton L. Sacco R.L. Saha S. Sampson U. Sanchez-Riera L. Sanman E. Schwebel D.C. Scott J.G. Segui-Gomez M. Shahraz S. Shepard D.S. Shin H. Shivakoti R. Silberberg D. Singh D. Singh G.M. Singh J.A. Singleton J. Sleet D.A. Sliwa K. Smith E. Smith J.L. Stapelberg N.J.C. Steer A. Steiner T. Stolk W.A. Stovner L.J. Sudfeld C. Syed S. Tamburlini G. Tavakkoli M. Taylor H.R. Taylor J.A. Taylor W.J. Thomas B. Thomson W.M. Thurston G.D. Tleyjeh I.M. Tonelli M. Towbin J.A. Truelsen T. Tsilimbaris M.K. Ubeda C. Undurraga E.A. van der Werf M.J. van Os J. Vavilala M.S. Venketasubramanian N. Wang M. Wang W. Watt K. Weatherall D.J. Weinstock M.A. Weintraub R. Weisskopf M.G. Weissman M.M. White R.A. Whiteford H. Wiebe N. Wiersma S.T. Wilkinson J.D. Williams H.C. Williams S.R.M. Witt E. Wolfe F. Woolf A.D. Wulf S. Yeh P-H. Zaidi A.K.M. Zheng Z-J. Zonies D. Lopez A.D. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012 380 9859 2197 2223 10.1016/S0140‑6736(12)61689‑4 23245608
    [Google Scholar]
  31. Stanaway J.D. Flaxman A.D. Naghavi M. Fitzmaurice C. Vos T. Abubakar I. Abu-Raddad L.J. Assadi R. Bhala N. Cowie B. Forouzanfour M.H. Groeger J. Hanafiah K.M. Jacobsen K.H. James S.L. MacLachlan J. Malekzadeh R. Martin N.K. Mokdad A.A. Mokdad A.H. Murray C.J.L. Plass D. Rana S. Rein D.B. Richardus J.H. Sanabria J. Saylan M. Shahraz S. So S. Vlassov V.V. Weiderpass E. Wiersma S.T. Younis M. Yu C. El Sayed Zaki M. Cooke G.S. The global burden of viral hepatitis from 1990 to 2013: Findings from the global burden of disease study 2013. Lancet 2016 388 10049 1081 1088 10.1016/S0140‑6736(16)30579‑7 27394647
    [Google Scholar]
  32. Franco E. Meleleo C. Serino L. Sorbara D. Zaratti L. Hepatitis A. Hepatitis A: Epidemiology and prevention in developing countries. World J. Hepatol. 2012 4 3 68 73 10.4254/wjh.v4.i3.68 22489258
    [Google Scholar]
  33. Jacobsen K.H. Wiersma S.T. Hepatitis A virus seroprevalence by age and world region, 1990 and 2005. Vaccine 2010 28 41 6653 6657 10.1016/j.vaccine.2010.08.037 20723630
    [Google Scholar]
  34. Papatheodoridis G.V. Sypsa V. Dalekos G. Yurdaydin C. van Boemmel F. Buti M. Goulis J. Calleja J.L. Chi H. Manolakopoulos S. Loglio A. Siakavellas S. Gatselis N. Keskın O. Lehretz M. Savvidou S. de la Revilla J. Hansen B.E. Kourikou A. Vlachogiannakos I. Galanis K. Idilman R. Colombo M. Esteban R. Janssen H.L.A. Berg T. Lampertico P. Eight-year survival in chronic hepatitis B patients under long-term entecavir or tenofovir therapy is similar to the general population. J. Hepatol. 2018 68 6 1129 1136 10.1016/j.jhep.2018.01.031 29427727
    [Google Scholar]
  35. Papatheodoridis G.V. Idilman R. Dalekos G.N. Buti M. Chi H. van Boemmel F. Calleja J.L. Sypsa V. Goulis J. Manolakopoulos S. Loglio A. Siakavellas S. Keskın O. Gatselis N. Hansen B.E. Lehretz M. de la Revilla J. Savvidou S. Kourikou A. Vlachogiannakos I. Galanis K. Yurdaydin C. Berg T. Colombo M. Esteban R. Janssen H.L.A. Lampertico P. The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B. Hepatology 2017 66 5 1444 1453 10.1002/hep.29320 28622419
    [Google Scholar]
  36. Broomé U. Olsson R. Lööf L. Bodemar G. Hultcrantz R. Danielsson A. Prytz H. Sandberg-Gertzén H. Wallerstedt S. Lindberg G. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 1996 38 4 610 615 10.1136/gut.38.4.610 8707097
    [Google Scholar]
  37. Negro F. Natural history of hepatic and extrahepatic hepatitis C virus diseases and impact of interferon-free HCV therapy. Cold Spring Harb. Perspect. Med. 2020 10 4 a036921 10.1101/cshperspect.a036921 31636094
    [Google Scholar]
  38. Kanwal F. Hoang T. Kramer J.R. Asch S.M. Goetz M.B. Zeringue A. Richardson P. El-Serag H.B. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection. Gastroenterology 2011 140 4 1182 1188.e1 10.1053/j.gastro.2010.12.032 21184757
    [Google Scholar]
  39. Hughes S.A. Wedemeyer H. Harrison P.M. Hepatitis delta virus. Lancet 2011 378 9785 73 85 10.1016/S0140‑6736(10)61931‑9 21511329
    [Google Scholar]
  40. Pascarella S. Negro F. Hepatitis D virus: An update. Liver Int. 2011 31 1 7 21 10.1111/j.1478‑3231.2010.02320.x 20880077
    [Google Scholar]
  41. Friedman LS Martin P Handbook of liver disease. Elsevier Health Sciences 2017
    [Google Scholar]
  42. World Health Organization Global hepatitis report 2017. World Health Organization 2017
    [Google Scholar]
  43. Asrani S.K. Devarbhavi H. Eaton J. Kamath P.S. Burden of liver diseases in the world. J. Hepatol. 2019 70 1 151 171 10.1016/j.jhep.2018.09.014 30266282
    [Google Scholar]
  44. Parkin D.M. Global cancer statistics in the year 2000. Lancet Oncol. 2001 2 9 533 543 10.1016/S1470‑2045(01)00486‑7 11905707
    [Google Scholar]
  45. Mitra A. Satelli A. Xia X. Cutrera J. Mishra L. Li S. Cell‐surface V imentin: A mislocalized protein for isolating csV imentin + CD 133 − novel stem‐like hepatocellular carcinoma cells expressing EMT markers. Int. J. Cancer 2015 137 2 491 496 10.1002/ijc.29382 25487874
    [Google Scholar]
  46. Arzumanyan A. Reis H.M.G.P.V. Feitelson M.A. Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat. Rev. Cancer 2013 13 2 123 135 10.1038/nrc3449 23344543
    [Google Scholar]
  47. Liao X. Bu Y. Jia Q. Traditional Chinese medicine as supportive care for the management of liver cancer: Past, present, and future. Genes Dis. 2020 7 3 370 379 10.1016/j.gendis.2019.10.016 32884991
    [Google Scholar]
  48. Chintana P. Role of curcumin on tumor angiogenesis in hepatocellular carcinoma. Naresuan Univ. J. Sci. Technol. 2008 16 3 239 254
    [Google Scholar]
  49. Lee E.O. Lee H.J. Hwang H.S. Ahn K.S. Chae C. Kang K.S. Lu J. Kim S.H. Potent inhibition of Lewis lung cancer growth by heyneanol A from the roots of Vitis amurensis through apoptotic and anti-angiogenic activities. Carcinogenesis 2006 27 10 2059 2069 10.1093/carcin/bgl055 16675471
    [Google Scholar]
  50. Khan N. Afaq F. Mukhtar H. Cancer chemoprevention through dietary antioxidants: Progress and promise. Antioxid. Redox Signal. 2008 10 3 475 510 10.1089/ars.2007.1740 18154485
    [Google Scholar]
  51. Yang C.S. Landau J.M. Huang M.T. Newmark H.L. Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu. Rev. Nutr. 2001 21 1 381 406 10.1146/annurev.nutr.21.1.381 11375442
    [Google Scholar]
  52. Mann C.D. Neal C.P. Garcea G. Manson M.M. Dennison A.R. Berry D.P. Phytochemicals as potential chemopreventive and chemotherapeutic agents in hepatocarcinogenesis. Eur. J. Cancer Prev. 2009 18 1 13 25 10.1097/CEJ.0b013e3282f0c090 19077560
    [Google Scholar]
  53. Mazzoccoli G. Miele L. Oben J. Grieco A. Vinciguerra M. Biology, epidemiology, clinical aspects of hepatocellular carcinoma and the role of sorafenib. Curr. Drug Targets 2016 17 7 783 799 10.2174/1389450117666151209120831 26648069
    [Google Scholar]
  54. van Malenstein H. Dekervel J. Verslype C. Van Cutsem E. Windmolders P. Nevens F. van Pelt J. Long-term exposure to sorafenib of liver cancer cells induces resistance with epithelial-to-mesenchymal transition, increased invasion and risk of rebound growth. Cancer Lett. 2013 329 1 74 83 10.1016/j.canlet.2012.10.021 23111106
    [Google Scholar]
  55. Llovet J.M. Montal R. Villanueva A. Randomized trials and endpoints in advanced HCC: Role of PFS as a surrogate of survival. J. Hepatol. 2019 70 6 1262 1277 10.1016/j.jhep.2019.01.028 30943423
    [Google Scholar]
  56. Reghupaty S.C. Sarkar D. Current status of gene therapy in hepatocellular carcinoma. Cancers 2019 11 9 1265 10.3390/cancers11091265 31466358
    [Google Scholar]
  57. Tai W.T. Chu P.Y. Shiau C.W. Chen Y.L. Li Y.S. Hung M.H. Chen L.J. Chen P.L. Su J.C. Lin P.Y. Yu H.C. Chen K.F. STAT3 mediates regorafenib-induced apoptosis in hepatocellular carcinoma. Clin. Cancer Res. 2014 20 22 5768 5776 10.1158/1078‑0432.CCR‑14‑0725 25248379
    [Google Scholar]
  58. Bruix J. Qin S. Merle P. Granito A. Huang Y.H. Bodoky G. Pracht M. Yokosuka O. Rosmorduc O. Breder V. Gerolami R. Masi G. Ross P.J. Song T. Bronowicki J.P. Ollivier-Hourmand I. Kudo M. Cheng A.L. Llovet J.M. Finn R.S. LeBerre M.A. Baumhauer A. Meinhardt G. Han G. RESORCE Investigators Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017 389 10064 56 66 10.1016/S0140‑6736(16)32453‑9 27932229
    [Google Scholar]
  59. Zhu X.D. Tang Z.Y. Sun H.C. Targeting angiogenesis for liver cancer: Past, present, and future. Genes Dis. 2020 7 3 328 335 10.1016/j.gendis.2020.03.010 32884987
    [Google Scholar]
  60. Zhou Y. Li Y. Zhou T. Zheng J. Li S. Li H.B. Dietary natural products for prevention and treatment of liver cancer. Nutrients 2016 8 3 156 10.3390/nu8030156 26978396
    [Google Scholar]
  61. Javaid A. Chaudhury F.A. Khan I.H. Ferdosi M.F.H. Potential health-related phytoconstituents in leaves of Chenopodium quinoa. Adv. Life Sci. 2022 9 4 574 578
    [Google Scholar]
  62. Ferdosi M.F.H. Javaid A. Khan I.H. Ferdosi M.F.A. Munir A. Bioactive components in methanolic flower extract of Ageratum conyzoides. Pak. J. Weed Sci. Res. 2021 27 2 181 190 10.28941/pjwsr.v27i2.954
    [Google Scholar]
  63. Naqvi S.F. Khan I.H. Javaid A. Hexane soluble bioactive components of Chenopodium murale STEM. Pak. J. Weed Sci. Res. 2021 27 2 425 432 10.28941/pjwsr.v26i4.875
    [Google Scholar]
  64. Iqbal J. Abbasi B.A. Mahmood T. Kanwal S. Ali B. Shah S.A. Khalil A.T. Plant-derived anticancer agents: A green anticancer approach. Asian Pac. J. Trop. Biomed. 2017 7 12 1129 1150 10.1016/j.apjtb.2017.10.016
    [Google Scholar]
  65. Schuppan D. Jia J.D. Brinkhaus B. Hahn E.G. Herbal products for liver diseases: A therapeutic challenge for the new millennium. Hepatology 1999 30 4 1099 1104 10.1002/hep.510300437 10498665
    [Google Scholar]
  66. Luk J.M. Wang X. Liu P. Wong K.F. Chan K.L. Tong Y. Hui C.K. Lau G.K. Fan S.T. Traditional Chinese herbal medicines for treatment of liver fibrosis and cancer: From laboratory discovery to clinical evaluation. Liver Int. 2007 27 7 879 890 10.1111/j.1478‑3231.2007.01527.x 17696925
    [Google Scholar]
  67. Sato H. Goto W. Yamamura J. Kurokawa M. Kageyama S. Takahara T. Watanabe A. Shiraki K. Therapeutic basis of glycyrrhizin on chronic hepatitis B. Antiviral Res. 1996 30 2-3 171 177 10.1016/0166‑3542(96)00942‑4 8783808
    [Google Scholar]
  68. Crance J.M. Lévêque F. Biziagos E. van Cuyck-Gandré H. Jouan A. Deloince R. Studies on mechanism of action of glycyrrhizin against hepatitis a virus replication in vitro. Antiviral Res. 1994 23 1 63 76 10.1016/0166‑3542(94)90033‑7 8141593
    [Google Scholar]
  69. Melhem A. Stern M. Shibolet O. Israeli E. Ackerman Z. Pappo O. Hemed N. Rowe M. Ohana H. Zabrecky G. Cohen R. Ilan Y. Treatment of chronic hepatitis C virus infection via antioxidants: Results of a phase I clinical trial. J. Clin. Gastroenterol. 2005 39 8 737 742 10.1097/01.mcg.0000174023.73472.29 16082287
    [Google Scholar]
  70. Hibasami H. Iwase H. Yoshioka K. Takahashi H. Glycyrrhetic acid (a metabolic substance and aglycon of glycyrrhizin) induces apoptosis in human hepatoma, promyelotic leukemia and stomach cancer cells. Int. J. Mol. Med. 2006 17 2 215 219 10.3892/ijmm.17.2.215 16391818
    [Google Scholar]
  71. Hsiang C.Y. Lai I.L. Chao D.C. Ho T.Y. Differential regulation of activator protein 1 activity by glycyrrhizin. Life Sci. 2002 70 14 1643 1656 10.1016/S0024‑3205(01)01556‑9 11991252
    [Google Scholar]
  72. Chen S.R. Dai Y. Zhao J. Lin L. Wang Y. Wang Y. A mechanistic overview of triptolide and celastrol, natural products from Tripterygium wilfordii Hook F. Front. Pharmacol. 2018 9 104 10.3389/fphar.2018.00104 29491837
    [Google Scholar]
  73. Kupchan S.M. Court W.A. Dailey R.G. Jr Gilmore C.J. Bryan R.F. Tumor inhibitors. LXXIV. Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii. J. Am. Chem. Soc. 1972 94 20 7194 7195 10.1021/ja00775a078 5072337
    [Google Scholar]
  74. Kupchan S.M. Schubert R.M. Selective alkylation: A biomimetic reaction of the antileukemic triptolides? Science 1974 185 4153 791 793 10.1126/science.185.4153.791 4843378
    [Google Scholar]
  75. Shamon L.A. Pezzuto J.M. Graves J.M. Mehta R.R. Wangcharoentrakul S. Sangsuwan R. Chaichana S. Tuchinda P. Cleason P. Reutrakul V. Evaluation of the mutagenic, cytotoxic, and antitumor potential of triptolide, a highly oxygenated diterpene isolated from Tripterygium wilfordii. Cancer Lett. 1997 112 1 113 117 10.1016/S0304‑3835(96)04554‑5 9029176
    [Google Scholar]
  76. Lee K.Y. Chang W. Qiu D. Kao P.N. Rosen G.D. PG490 (triptolide) cooperates with tumor necrosis factor-α to induce apoptosis in tumor cells. J. Biol. Chem. 1999 274 19 13451 13455 10.1074/jbc.274.19.13451 10224110
    [Google Scholar]
  77. Wai-Ching Chan E. Chak-Sum Cheng S. Wan-Yee Sin F. Xie Y. Triptolide induced cytotoxic effects on human promyelocytic leukemia, T cell lymphoma and human hepatocellular carcinoma cell lines. Toxicol. Lett. 2001 122 1 81 87 10.1016/S0378‑4274(01)00353‑8 11397559
    [Google Scholar]
  78. Feng L. Zhang D. Fan C. Ma C. Yang W. Meng Y. Wu W. Guan S. Jiang B. Yang M. Liu X. Guo D. ER stress-mediated apoptosis induced by celastrol in cancer cells and important role of glycogen synthase kinase-3β in the signal network. Cell Death Dis. 2013 4 7 e715 10.1038/cddis.2013.222 23846217
    [Google Scholar]
  79. Chang W. He W. Li P.P. Song S.S. Yuan P.F. Lu J.T. Wei W. Protective effects of Celastrol on diethylnitrosamine-induced hepatocellular carcinoma in rats and its mechanisms. Eur. J. Pharmacol. 2016 784 173 180 10.1016/j.ejphar.2016.04.045 27181068
    [Google Scholar]
  80. Shen Y. Zhang X. Wang Y. Cao F. Uzan G. Peng B. Zhang D. Celastrol targets IRAKs to block Toll-like receptor 4-mediated nuclear factor-κB activation. J. Integr. Med. 2016 14 3 203 208 10.1016/S2095‑4964(16)60257‑1 27181127
    [Google Scholar]
  81. Yan Y.Y. Guo Y. Zhang W. Ma C.G. Zhang Y.X. Wang C. Wang H.X. Celastrol enhanced the anticancer effect of lapatinib in human hepatocellular carcinoma cells in vitro. J. BUON 2014 19 2 412 418 24965400
    [Google Scholar]
  82. Tan W. Li Y. Chen M. Wang Y. Berberine hydrochloride: Anticancer activity and nanoparticulate delivery system. Int. J. Nanomedicine 2011 6 1773 1777 10.2147/IJN.S22683 21931477
    [Google Scholar]
  83. Maiti M. Kumar G.S. Polymorphic nucleic Acid binding of bioactive isoquinoline alkaloids and their role in cancer. J. Nucleic Acids 2010 2010 1 593408 10.4061/2010/593408 20814427
    [Google Scholar]
  84. Bhadra K. Kumar G.S. Therapeutic potential of nucleic acid‐binding isoquinoline alkaloids: Binding aspects and implications for drug design. Med. Res. Rev. 2011 31 6 821 862 10.1002/med.20202 20077560
    [Google Scholar]
  85. Peng PL Kuo WH Tseng HC Chou FP Synergistic tumor-killing effect of radiation and berberine combined treatment in lung cancer: The contribution of autophagic cell death. Int. J. Radiat. Oncol. Biol. Phys. 2008 Feb 70 2 529 542 10.1016/j.ijrobp.2007.08.034
    [Google Scholar]
  86. Meng Z. Li T. Ma X. Wang X. Van Ness C. Gan Y. Zhou H. Tang J. Lou G. Wang Y. Wu J. Yen Y. Xu R. Huang W. Berbamine inhibits the growth of liver cancer cells and cancer-initiating cells by targeting Ca²⁺/calmodulin-dependent protein kinase II. Mol. Cancer Ther. 2013 12 10 2067 2077 10.1158/1535‑7163.MCT‑13‑0314 23960096
    [Google Scholar]
  87. Sharma S. Tanwar A. Gupta D.K. Curcumin: An adjuvant therapeutic remedy for liver cancer. Hepatoma Res. 2016 2 3 62 70 10.20517/2394‑5079.2015.59
    [Google Scholar]
  88. Cui S.X. Qu X.J. Xie Y.Y. Zhou L. Nakata M. Makuuchi M. Tang W. Curcumin inhibits telomerase activity in human cancer cell lines. Int. J. Mol. Med. 2006 18 2 227 231 10.3892/ijmm.18.2.227 16820928
    [Google Scholar]
  89. Nasr M. Selima E. Hamed O. Kazem A. Targeting different angiogenic pathways with combination of curcumin, leflunomide and perindopril inhibits diethylnitrosamine-induced hepatocellular carcinoma in mice. Eur. J. Pharmacol. 2014 723 267 275 10.1016/j.ejphar.2013.11.022 24291100
    [Google Scholar]
  90. Ziegler D.S. Kung A.L. Therapeutic targeting of apoptosis pathways in cancer. Curr. Opin. Oncol. 2008 20 1 97 103 10.1097/CCO.0b013e3282f310f6 18043263
    [Google Scholar]
  91. Liu H. Liang Y. Wang L. Tian L. Song R. Han T. Pan S. Liu L. In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog. PLoS One 2012 7 10 e48075 10.1371/journal.pone.0048075 23118928
    [Google Scholar]
  92. Yu J. Zhou X. He X. Dai M. Zhang Q. Curcumin induces apoptosis involving bax/bcl-2 in human hepatoma SMMC-7721 cells. Asian Pac. J. Cancer Prev. 2011 12 8 1925 1929 22292626
    [Google Scholar]
  93. Cao J. Jia L. Zhou H.M. Liu Y. Zhong L.F. Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells. Toxicol. Sci. 2006 91 2 476 483 10.1093/toxsci/kfj153 16537656
    [Google Scholar]
  94. El Khawand T. Courtois A. Valls J. Richard T. Krisa S. A review of dietary stilbenes: Sources and bioavailability. Phytochem. Rev. 2018 17 5 1007 1029 10.1007/s11101‑018‑9578‑9
    [Google Scholar]
  95. Aja I. Ruiz-Larrea M.B. Courtois A. Krisa S. Richard T. Ruiz-Sanz J.I. Screening of natural stilbene oligomers from Vitis vinifera for anticancer activity on human hepatocellular carcinoma cells. Antioxidants 2020 9 6 469 10.3390/antiox9060469 32492881
    [Google Scholar]
  96. Liao S. Liu J. Xu M. Zheng J. Evaluation of the liver cancer prevention of anthocyanin extracts from mulberry (Morus alba L.) variety PR-01. Adv. Biosci. Biotechnol. 2018 9 9 423 442 10.4236/abb.2018.99030
    [Google Scholar]
  97. Li D. Wang P. Luo Y. Zhao M. Chen F. Health benefits of anthocyanins and molecular mechanisms: Update from recent decade. Crit. Rev. Food Sci. Nutr. 2017 57 8 1729 1741 10.1080/10408398.2015.1030064 26192537
    [Google Scholar]
  98. Bimonte S. Cascella M. Schiavone V. Mehrabi-Kermani F. Cuomo A. The roles of epigallocatechin-3-gallate in the treatment of neuropathic pain: An update on preclinical in vivo studies and future perspectives. Drug Des. Devel. Ther. 2017 11 2737 2742 10.2147/DDDT.S142475 29066865
    [Google Scholar]
  99. Liu A.B. Tao S. Lee M.J. Hu Q. Meng X. Lin Y. Yang C.S. Effects of gut microbiota and time of treatment on tissue levels of green tea polyphenols in mice. Biofactors 2018 44 4 348 360 10.1002/biof.1430 29740891
    [Google Scholar]
  100. Bimonte S. Albino V. Piccirillo M. Nasto A. Molino C. Palaia R. Cascella M. Epigallocatechin-3-gallate in the prevention and treatment of hepatocellular carcinoma: experimental findings and translational perspectives. Drug Des. Devel. Ther. 2019 13 611 621 10.2147/DDDT.S180079 30858692
    [Google Scholar]
  101. Nambiar D.M. Kumari J. Arya G.C. Singh A.K. Bisht N.C. A cell suspension based uptake method to study high affinity glucosinolate transporters. Plant Methods 2020 16 1 75 10.1186/s13007‑020‑00618‑0 32489397
    [Google Scholar]
  102. Gu H. Mao X. Du M. Metabolism, absorption, and anti-cancer effects of sulforaphane: An update. Crit. Rev. Food Sci. Nutr. 2022 62 13 3437 3452 10.1080/10408398.2020.1865871 33393366
    [Google Scholar]
  103. Mastuo T. Miyata Y. Yuno T. Mukae Y. Otsubo A. Mitsunari K. Ohba K. Sakai H. Molecular mechanisms of the anti-cancer effects of isothiocyanates from cruciferous vegetables in bladder cancer. Molecules 2020 25 3 575 10.3390/molecules25030575 32013065
    [Google Scholar]
  104. Mitsiogianni M. Koutsidis G. Mavroudis N. Trafalis D.T. Botaitis S. Franco R. Zoumpourlis V. Amery T. Galanis A. Pappa A. Panayiotidis M.I. The role of isothiocyanates as cancer chemo-preventive, chemo-therapeutic and anti-melanoma agents. Antioxidants 2019 8 4 106 10.3390/antiox8040106 31003534
    [Google Scholar]
  105. Zhang Y. Huang H. Jin L. Lin S. Anticarcinogenic effects of isothiocyanates on hepatocellular carcinoma. Int. J. Mol. Sci. 2022 23 22 13834 10.3390/ijms232213834 36430307
    [Google Scholar]
  106. Mekuria A.N. Tura A.K. Hagos B. Sisay M. Abdela J. Mishore K.M. Motbaynor B. Anti-cancer effects of lycopene in animal models of hepatocellular carcinoma: A systematic review and meta-analysis. Front. Pharmacol. 2020 11 1306 10.3389/fphar.2020.01306 32982734
    [Google Scholar]
  107. Stice C.P. Xia H. Wang X.D. Tomato lycopene prevention of alcoholic fatty liver disease and hepatocellular carcinoma development. Chronic Dis. Transl. Med. 2018 4 4 211 224 10.1016/j.cdtm.2018.11.001 30603740
    [Google Scholar]
  108. Stice C.P. Liu C. Aizawa K. Greenberg A.S. Ausman L.M. Wang X.D. Dietary tomato powder inhibits alcohol-induced hepatic injury by suppressing cytochrome p450 2E1 induction in rodent models. Arch. Biochem. Biophys. 2015 572 81 88 10.1016/j.abb.2015.01.004 25592162
    [Google Scholar]
  109. Xiang J. Xiang Y. Lin S. Xin D. Liu X. Weng L. Chen T. Zhang M. Anticancer effects of deproteinized asparagus polysaccharide on hepatocellular carcinoma in vitro and in vivo. Tumour Biol. 2014 35 4 3517 3524 10.1007/s13277‑013‑1464‑x 24310501
    [Google Scholar]
  110. Weng L.L. Xiang J.F. Lin J.B. Yi S.H. Yang L.T. Li Y.S. Zeng H.T. Lin S.M. Xin D.W. Zhao H.L. Qiu S.Q. Chen T. Zhang M.G. Asparagus polysaccharide and gum with hepatic artery embolization induces tumor growth and inhibits angiogenesis in an orthotopic hepatocellular carcinoma model. Asian Pac. J. Cancer Prev. 2015 15 24 10949 10955 10.7314/APJCP.2014.15.24.10949 25605207
    [Google Scholar]
  111. Cheng W. Cheng Z. Xing D. Zhang M. Asparagus polysaccharide suppresses the migration, invasion, and angiogenesis of hepatocellular carcinoma cells partly by targeting the HIF-1 α /VEGF signalling pathway in vitro. Evid. Based Complement. Alternat. Med. 2019 2019 1 1 10 10.1155/2019/3769879 31239858
    [Google Scholar]
  112. Al-Fatlawi A.A. Al-Fatlawi A.A. Irshad M. Zafaryab M. Alam Rizvi M.M. Ahmad A. Rice bran phytic acid induced apoptosis through regulation of Bcl-2/Bax and p53 genes in HepG2 human hepatocellular carcinoma cells. Asian Pac. J. Cancer Prev. 2014 15 8 3731 3736 10.7314/APJCP.2014.15.8.3731 24870784
    [Google Scholar]
  113. Al-Fatlawi A.A. Rizvi M.M. Ahmad A.Y. Anticarcinogenic activity of rice bran phytic acid against human breast cancer cell line (MCF-7). Asian J. Pharm. Clin. Res. 2014 7 1 151 155
    [Google Scholar]
  114. Abdulwaliyu I. Arekemase S.O. Adudu J.A. Batari M.L. Egbule M.N. Okoduwa S.I.R. Investigation of the medicinal significance of phytic acid as an indispensable anti-nutrient in diseases. Clin. Nutr. Exp. 2019 28 42 61 10.1016/j.yclnex.2019.10.002
    [Google Scholar]
  115. Pujol A. Sanchis P. Grases F. Masmiquel L. Phytate intake, health and disease:“let thy food be thy medicine and medicine be thy food”. Antioxidants 2023 12 1 146 10.3390/antiox12010146 36671007
    [Google Scholar]
  116. Prasad S. Tyagi A.K. Ginger and its constituents: Role in prevention and treatment of gastrointestinal cancer. Gastroenterol. Res. Pract. 2015 2015 1 1 11 10.1155/2015/142979 25838819
    [Google Scholar]
  117. Gautam A.K. Sharma D. Sharma J. Saini K.C. Legume lectins: Potential use as a diagnostics and therapeutics against the cancer. Int. J. Biol. Macromol. 2020 142 474 483 10.1016/j.ijbiomac.2019.09.119 31593731
    [Google Scholar]
  118. Jian Q. Yang Z. Shu J. Liu X. Zhang J. Li Z. Lectin BS‐I inhibits cell migration and invasion via AKT/GSK‐3β/β‐catenin pathway in hepatocellular carcinoma. J. Cell. Mol. Med. 2018 22 1 315 329 10.1111/jcmm.13320 28922551
    [Google Scholar]
  119. Lee T.K.W. Castilho A. Cheung V.C.H. Tang K.H. Ma S. Ng I.O.L. Lupeol targets liver tumor-initiating cells through phosphatase and tensin homolog modulation. Hepatology 2011 53 1 160 170 10.1002/hep.24000 20979057
    [Google Scholar]
  120. Eldohaji L.M. Fayed B. Hamoda A.M. Ershaid M. Abdin S. Alhamidi T.B. Mohammad M.G. Omar H.A. Soliman S.S.M. Potential targeting of Hep3B liver cancer cells by lupeol isolated from Avicennia marina. Arch. Pharm. 2021 354 9 2100120 10.1002/ardp.202100120 34085721
    [Google Scholar]
  121. Wang L. Huang W. Zhan J. Grape seed proanthocyanidins induce autophagy and modulate survivin in HepG2 cells and inhibit xenograft tumor growth in vivo. Nutrients 2019 11 12 2983 10.3390/nu11122983 31817589
    [Google Scholar]
  122. Wang L. Zhan J. Huang W. Grape seed proanthocyanidins induce apoptosis and cell cycle arrest of HepG2 cells accompanied by induction of the MAPK pathway and NAG-1. Antioxidants 2020 9 12 1200 10.3390/antiox9121200 33260632
    [Google Scholar]
  123. Gong G. Guan Y.Y. Zhang Z.L. Rahman K. Wang S.J. Zhou S. Luan X. Zhang H. Isorhamnetin: A review of pharmacological effects. Biomed. Pharmacother. 2020 128 110301 10.1016/j.biopha.2020.110301 32502837
    [Google Scholar]
  124. Zhang Z. Chen S. Mei H. Xuan J. Guo X. Couch L. Dobrovolsky V.N. Guo L. Mei N. Ginkgo biloba leaf extract induces DNA damage by inhibiting topoisomerase II activity in human hepatic cells. Sci. Rep. 2015 5 1 14633 10.1038/srep14633 26419945
    [Google Scholar]
  125. Runhuan F. Haiyan W. Quantitative proteomic analysis of Isorhamnetin treatment in human liver cancer cells. J. Med. Plants Res. 2018 12 7 77 88 10.5897/JMPR2018.6561
    [Google Scholar]
  126. Ko J.H. Sethi G. Um J.Y. Shanmugam M.K. Arfuso F. Kumar A.P. Bishayee A. Ahn K.S. The role of resveratrol in cancer therapy. Int. J. Mol. Sci. 2017 18 12 2589 10.3390/ijms18122589 29194365
    [Google Scholar]
  127. Polachi N. Bai G. Li T. Chu Y. Wang X. Li S. Gu N. Wu J. Li W. Zhang Y. Zhou S. Sun H. Liu C. Modulatory effects of silibinin in various cell signaling pathways against liver disorders and cancer – A comprehensive review. Eur. J. Med. Chem. 2016 123 577 595 10.1016/j.ejmech.2016.07.070 27517806
    [Google Scholar]
  128. Tiwari P. Mishra K. Silibinin in cancer therapy: A promising prospect. Cancer Res. Front. 2015 1 3 303 318 10.17980/2015.303
    [Google Scholar]
  129. Gu H.R. Park S.C. Choi S.J. Lee J.C. Kim Y.C. Han C.J. Kim J. Yang K.Y. Kim Y.J. Noh G.Y. No S.H. Jeong J.H. Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells. Clin. Mol. Hepatol. 2015 21 1 49 59 10.3350/cmh.2015.21.1.49 25834802
    [Google Scholar]
  130. Li F. Jiang T. Li Q. Ling X. Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: Did we miss something in CPT analogue molecular targets for treating human disease such as cancer? Am. J. Cancer Res. 2017 7 12 2350 2394 29312794
    [Google Scholar]
  131. Kciuk M. Marciniak B. Kontek R. Irinotecan—still an important player in cancer chemotherapy: A comprehensive overview. Int. J. Mol. Sci. 2020 21 14 4919 10.3390/ijms21144919 32664667
    [Google Scholar]
  132. Cinelli M.A. Morrell A.E. Dexheimer T.S. Agama K. Agrawal S. Pommier Y. Cushman M. The structure–activity relationships of A-ring-substituted aromathecin topoisomerase I inhibitors strongly support a camptothecin-like binding mode. Bioorg. Med. Chem. 2010 18 15 5535 5552 10.1016/j.bmc.2010.06.040 20630766
    [Google Scholar]
  133. Brandi G. Biasco G. Mirarchi M.G. Golfieri R. Di Paolo A. Borghi A. Fanello S. Derenzini E. Agostini V. Giampalma E. Cappelli A. Pini P. Costantini S. Danesi R. Bolondi L. Piscaglia F. A phase I study of continuous hepatic arterial infusion of Irinotecan in patients with locally advanced hepatocellular carcinoma. Dig. Liver Dis. 2011 43 12 1015 1021 10.1016/j.dld.2011.08.005 21917536
    [Google Scholar]
  134. Zhang Y. Feng L. Zhong X. Wang L. Chang J. Vincristine and irinotecan in children with relapsed hepatoblastoma: A single-institution experience. Pediatr. Hematol. Oncol. 2015 32 1 18 25 10.3109/08880018.2014.909913 24852330
    [Google Scholar]
  135. Zsíros J. Brugières L. Brock P. Roebuck D. Maibach R. Child M. Morland B. Casanova M. Pariente D. Paris C. Camargo B. Ronghe M. Zimmermann A. Plaschkes J. Czauderna P. Perilongo G. Efficacy of irinotecan single drug treatment in children with refractory or recurrent hepatoblastoma – A phase II trial of the childhood liver tumour strategy group (SIOPEL). Eur. J. Cancer 2012 48 18 3456 3464 10.1016/j.ejca.2012.06.023 22835780
    [Google Scholar]
  136. Nicolle D. Fabre M. Simon-Coma M. Gorse A. Kappler R. Nonell L. Mallo M. Haidar H. Déas O. Mussini C. Guettier C. Redon M.J. Brugières L. Ghigna M.R. Fadel E. Galmiche-Rolland L. Chardot C. Judde J.G. Armengol C. Branchereau S. Cairo S. Patient‐derived mouse xenografts from pediatric liver cancer predict tumor recurrence and advise clinical management. Hepatology 2016 64 4 1121 1135 10.1002/hep.28621 27115099
    [Google Scholar]
  137. Zhao H. Guo Y. Li S. Han R. Ying J. Zhu H. Wang Y. Yin L. Han Y. Sun L. Wang Z. Lin Q. Bi X. Jiao Y. Jia H. Zhao J. Huang Z. Li Z. Zhou J. Song W. Meng K. Cai J. A novel anti-cancer agent Icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the IL-6/Jak2/Stat3 pathway. Oncotarget 2015 6 31 31927 31943 10.18632/oncotarget.5578 26376676
    [Google Scholar]
  138. Tan H.L. Chan K.G. Pusparajah P. Saokaew S. Duangjai A. Lee L.H. Goh B.H. Anti-cancer properties of the naturally occurring aphrodisiacs: Icaritin and its derivatives. Front. Pharmacol. 2016 7 191 10.3389/fphar.2016.00191 27445824
    [Google Scholar]
  139. Fan Y Y. First-in-class immune-modulating small molecule Icaritin in advanced hepatocellular carcinoma: Preliminary results of safety, durable survival and immune biomarkers. BMC Cancer 2019 19 1 1
    [Google Scholar]
  140. Bailly C. Molecular and cellular basis of the anticancer activity of the prenylated flavonoid icaritin in hepatocellular carcinoma. Chem. Biol. Interact. 2020 325 109124 10.1016/j.cbi.2020.109124 32437694
    [Google Scholar]
  141. Qin S.K. Li Q. Ming Xu J. Liang J. Cheng Y. Fan Y. Jiang J. Ye H. Tao H. Li L. Zheng L. Wei Z. Li S. Meng K. Ye B. Sun Y. Icaritin‐induced immunomodulatory efficacy in advanced hepatitis B virus‐related hepatocellular carcinoma: Immunodynamic biomarkers and overall survival. Cancer Sci. 2020 111 11 4218 4231 10.1111/cas.14641 32889778
    [Google Scholar]
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