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image of Antitumor and Immunoregulatory Effects of Curcumin Analog, (Z)-3-Hydroxy-1-(2-hydroxyphenyl)-3-phenyl prop-2-ene-1-one (DK1), on CT26-Tumor-Bearing BALB/c Mice

Abstract

Introduction

, commonly known as turmeric, contains curcumin, which is its main compound and has been reported to possess a wide variety of pharmacological activities, such as anti-carcinogenic, anti-malarial, antioxidant, antibacterial, anti-mutagenic, anti-inflammatory, and immunomodulatory effects. Even though it has many strong biological properties, curcumin lacks solubility, which affects its clinical efficacy. DK1 is a curcumin analogue that has been found to possess selective cytotoxicity on breast cancer cells compared to normal breast cells; however, its effectiveness in colon cancer has yet to be validated. This study was performed to investigate the effects of DK1 on colon cancer using an model in terms of its anti-apoptotic, immunoregulatory, and antioxidant potential. The pathways affected by the DK1 treatment were also evaluated.

Methods

In this study, male BALB/c mice induced with colon cancer were utilized, and the resulting tumours and spleen were subjected to TUNEL, immunophenotyping, and several antioxidant assays, such as nitric oxide, malondialdehyde, and superoxide dismutase, as well as gene and protein expression analyses.

Results

K1 treatment led to tumor shrinkage, an increase in apoptotic tumor cells, and elevated populations of helper and cytotoxic T cells by 5% and 3%, respectively. Besides that, the NO and MDA levels were also significantly reduced. This study also observed dysregulations in several oncogenes in the VEGF pathway, such as CMYC, iNOS, and IL-1β genes, which are involved in angiogenesis and inflammation.

Discussion

The effects of DK1 treatment included antitumor and anti-inflammatory properties against the inoculated CT26 tumour. DK1 showed potential in regulating the inflammation the VEGF pathway by the significant downregulation of TNF-α and IL-1β pro-inflammatory genes, as well as PTX3, OPN, and serpin-E1 pro-angiogenic proteins.

Conclusion

The results suggested that DK1 may potentially function as an immunoregulator and anti-cancer agent for colon cancer therapy.

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2025-10-24
2026-02-20

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References

  1. Muhamad N.A. Ma’amor N.H. Rosli I.A. Leman F.N. Abdul Mutalip M.H. Chan H.K. Yusof S.N. Tamin N.S.I. Aris T. Lai N.M. Abu Hassan M.R. Colorectal cancer survival among Malaysia population: Data from the Malaysian National Cancer Registry. Front Oncol 2023 13 1132417 10.3389/fonc.2023.1132417 38094603
    [Google Scholar]
  2. Bray F. Laversanne M. Sung H. Ferlay J. Siegel R.L. Soerjomataram I. Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. Cancer. J. Clin. 2024 74 3 229 263 10.3322/caac.21834 38572751
    [Google Scholar]
  3. Zahed H. Feng X. Sheikh M. Bray F. Ferlay J. Ginsburg O. Shiels M.S. Robbins H.A. Age at diagnosis for lung, colon, breast and prostate cancers: An international comparative study. Int. J. Cancer. 2024 154 1 28 40 10.1002/ijc.34671 37615573
    [Google Scholar]
  4. Yamamoto T. Kawada K. Obama K. Inflammation-related biomarkers for the prediction of prognosis in colorectal cancer patients. Int. J. Mol. Sci. 2021 22 15 8002 10.3390/ijms22158002 34360768
    [Google Scholar]
  5. Shah S.C. Itzkowitz S.H. Colorectal cancer in inflammatory bowel disease: Mechanisms and management. Gastroenterology 2022 162 3 715 730.e3 10.1053/j.gastro.2021.10.035 34757143
    [Google Scholar]
  6. Shen H. Shen J. Pan H. Xu L. Sheng H. Liu B. Yao M. Curcumin analog B14 has high bioavailability and enhances the effect of anti-breast cancer cells in vitro and in vivo. Cancer Sci 2021 112 2 815 827 10.1111/cas.14770 33316116
    [Google Scholar]
  7. Kaur K. Al-Khazaleh A.K. Bhuyan D.J. Li F. Li C.G. A review of recent curcumin analogues and their antioxidant, anti-inflammatory, and anticancer activities. Antioxidants 2024 13 9 1092 10.3390/antiox13091092 39334750
    [Google Scholar]
  8. Valiveti C.K. Kumar B. Singh A.D. Biradar S.K. Ahmad R. Singh A.B. Tummala H. Stable dietary ora-curcumin formulation protects from experimental colitis and colorectal cancer. Cells 2024 13 11 957 10.3390/cells13110957 38891089
    [Google Scholar]
  9. Chandan S. Mohan B.P. Chandan O.C. Ahmad R. Challa A. Tummala H. Singh S. Dhawan P. Ponnada S. Singh A.B. Adler D.G. Curcumin use in ulcerative colitis: Is it ready for prime time? A systematic review and meta-analysis of clinical trials. Ann. Gastroenterol 2019 33 1 53 58 10.20524/aog.2019.0439 31892798
    [Google Scholar]
  10. Clariano M. Marques V. Vaz J. Awam S. Afonso M.B. Jesus Perry M. Rodrigues C.M.P. Monocarbonyl analogs of curcumin with potential to treat colorectal cancer. Chem. Biodivers 2023 20 3 202300222 10.1002/cbdv.202300222 36807727
    [Google Scholar]
  11. Liu G. Chen J. Bao Z. Promising antitumor effects of the curcumin analog DMC-BH on colorectal cancer cells. Aging 2023 15 6 2221 2236 10.18632/aging.204610 36971681
    [Google Scholar]
  12. Wulandari F. Ikawati M. Widyarini S. Kirihata M. Novitasari D. Kato J. Meiyanto E. Tumour-suppressive effects of curcumin analogs CCA-1.1 and Pentagamavunone-1 in colon cancer: In vivo and in vitro studies. J Adv Pharm Technol Res 2023 14 4 317 324 10.4103/JAPTR.JAPTR_315_23 38107450
    [Google Scholar]
  13. Lambring C. Varga K. Livingston K. Lorusso N. Dudhia A. Basha R. Therapeutic applications of curcumin and derivatives in colorectal cancer. Onco. Ther. 2022 9 1 51 62 10.1615/OncoTherap.2022044575 37324055
    [Google Scholar]
  14. Herrero de la Parte B. Rodeño-Casado M. Iturrizaga Correcher S. Mar Medina C. García-Alonso I. Curcumin reduces colorectal cancer cell proliferation and migration and slows in vivo growth of liver metastases in rats. Biomedicines 2021 9 9 1183 10.3390/biomedicines9091183 34572369
    [Google Scholar]
  15. Hussin Y. Aziz M. Che Rahim N. Yeap S. Mohamad N. Masarudin M. Nordin N. Abd Rahman N. Yong C. Akhtar M. Zamrus S. Alitheen N. DK1 induces apoptosis via mitochondria-dependent signaling pathway in human colon carcinoma cell lines in vitro. Int. J. Mol. Sci. 2018 19 4 1151 10.3390/ijms19041151 29641445
    [Google Scholar]
  16. Karthika C. Hari B. Mano V. Radhakrishnan A. Janani S.K. Akter R. Kaushik D. Rahman M.H. Curcumin as a great contributor for the treatment and mitigation of colorectal cancer. Exp. Gerontol 2021 152 111438 10.1016/j.exger.2021.111438 34098006
    [Google Scholar]
  17. Aziz M.N.M. Rahim N.F.C. Hussin Y. Yeap S.K. Masarudin M.J. Mohamad N.E. Akhtar M.N. Osman M.A. Cheah Y.K. Alitheen N.B. Anti-metastatic and anti-angiogenic effects of curcumin analog DK1 on human osteosarcoma cells in vitro. Pharmaceuticals 2021 14 6 532 10.3390/ph14060532 34204873
    [Google Scholar]
  18. Aziz M. Hussin Y. Che Rahim N. Nordin N. Mohamad N. Yeap S. Yong C. Masarudin M. Cheah Y. Abu N. Akhtar M. Alitheen N. Curcumin analog DK1 induces apoptosis in human osteosarcoma cells in vitro through mitochondria-dependent signaling pathway. Molecules 2018 23 1 75 10.3390/molecules23010075 29303982
    [Google Scholar]
  19. Ali N.M. Yeap S.K. Abu N. Lim K.L. Ky H. Pauzi A.Z.M. Ho W.Y. Tan S.W. Alan-Ong H.K. Zareen S. Alitheen N.B. Akhtar M.N. Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells. Cancer Cell Int. 2017 17 1 30 10.1186/s12935‑017‑0400‑3 28239299
    [Google Scholar]
  20. González-Gualda E. Baker A.G. Fruk L. Muñoz-Espín D. A guide to assessing cellular senescence in vitro and in vivo. FEBS J 2021 288 1 56 80 10.1111/febs.15570 32961620
    [Google Scholar]
  21. Lannagan T.R.M. Jackstadt R. Leedham S.J. Sansom O.J. Advances in colon cancer research: in vitro and animal models. Curr. Opin. Genet. Dev. 2021 66 50 56 10.1016/j.gde.2020.12.003 33422950
    [Google Scholar]
  22. Brough D. Amos H. Turley K. Murkin J. Trends in subcutaneous tumour height and impact on measurement accuracy. Cancer Inform 2023 22 11769351231165181 10.1177/11769351231165181 37113645
    [Google Scholar]
  23. Guide for the Care and Use of Laboratory Animals. 8th edition. Washington (DC): National Academies Press (US); 2011. Available from: https://www.ncbi.nlm.nih.gov/books/NBK54050/ 10.17226/12910
  24. Lin L. Liu Y. Li H. Li P-K. Fuchs J. Shibata H. Iwabuchi Y. Lin J. Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030. Br. J. Cancer 2011 105 2 212 220 10.1038/bjc.2011.200 21694723
    [Google Scholar]
  25. Najmuddin S.U.F.S. Amin Z.M. Tan S.W. Yeap S.K. Kalyanasundram J. Ani M.A.C. Veerakumarasivam A. Chan S.C. Chia S.L. Yusoff K. Alitheen N.B. Cytotoxicity study of the interleukin-12-expressing recombinant Newcastle disease virus strain, rAF-IL12, towards CT26 colon cancer cells in vitro and in vivo. Cancer Cell Int 2020 20 1 278 10.1186/s12935‑020‑01372‑y 32612457
    [Google Scholar]
  26. Rajamanickam V. Yan T. Wu L. Zhao Y. Xu X. Zhu H. Chen X. Wang M. Liu Z. Liu Z. Liang G. Wang Y. Allylated curcumin analog CA6 inhibits TrxR1 and leads to ROS-dependent apoptotic cell death in gastric cancer through Akt-FoxO3a. Cancer Manag Res. 2020 12 247 263 10.2147/CMAR.S227415 32021440
    [Google Scholar]
  27. Fioranelli M. Roccia M.G. Flavin D. Cota L. Regulation of inflammatory reaction in health and disease. Int. J. Mol. Sci. 2021 22 10 5277 10.3390/ijms22105277 34067872
    [Google Scholar]
  28. Alberts B. Johnson A. Lewis J. Helper T cells and lymphocyte activation. Molecular biology of the cell Garland Science 2002 4th ed
    [Google Scholar]
  29. Tay R.E. Richardson E.K. Toh H.C. Revisiting the role of CD4+ T cells in cancer immunotherapy—new insights into old paradigms. Cancer Gene Ther 2021 28 1-2 5 17 10.1038/s41417‑020‑0183‑x 32457487
    [Google Scholar]
  30. Seddiki N. Santner-Nanan B. Tangye S.G. Alexander S.I. Solomon M. Lee S. Nanan R. de Saint Groth B.F. Persistence of naive CD45RA+ regulatory T cells in adult life. Blood 2006 107 7 2830 2838 10.1182/blood‑2005‑06‑2403 16332974
    [Google Scholar]
  31. Shih K.C. Chan H.W. Wu C.Y. Chuang H.Y. Curcumin enhances the abscopal effect in mice with colorectal cancer by acting as an immunomodulator. Pharmaceutics 2023 15 5 1519 10.3390/pharmaceutics15051519 37242761
    [Google Scholar]
  32. Pakiet A. Kobiela J. Stepnowski P. Sledzinski T. Mika A. Changes in lipids composition and metabolism in colorectal cancer: A review. Lipids Health Dis. 2019 18 1 29 10.1186/s12944‑019‑0977‑8 30684960
    [Google Scholar]
  33. Satoh K. Yachida S. Sugimoto M. Oshima M. Nakagawa T. Akamoto S. Tabata S. Saitoh K. Kato K. Sato S. Igarashi K. Aizawa Y. Kajino-Sakamoto R. Kojima Y. Fujishita T. Enomoto A. Hirayama A. Ishikawa T. Taketo M.M. Kushida Y. Haba R. Okano K. Tomita M. Suzuki Y. Fukuda S. Aoki M. Soga T. Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC. Proc. Natl. Acad. Sci. USA. 2017 114 37 E7697 E7706 10.1073/pnas.1710366114 28847964
    [Google Scholar]
  34. Clemente S.M. Martínez-Costa O.H. Monsalve M. Samhan-Arias A.K. Targeting lipid peroxidation for cancer treatment. Molecules 2020 25 21 5144 10.3390/molecules25215144 33167334
    [Google Scholar]
  35. Chaiswing L. St Clair W.H. St Clair D.K. Redox paradox: A novel approach to therapeutics-resistant cancer. Antioxid Redox Signal 2018 29 13 1237 1272 10.1089/ars.2017.7485 29325444
    [Google Scholar]
  36. Condello M. Meschini S. Role of natural antioxidant products in colorectal cancer disease: A focus on a natural compound derived from Prunus spinosa, trigno ecotype. Cells 2021 10 12 3326 10.3390/cells10123326 34943833
    [Google Scholar]
  37. Bardelčíková A. Šoltys J. Mojžiš J. Oxidative stress, inflammation and colorectal cancer: An overview. Antioxidants 2023 12 4 901 10.3390/antiox12040901 37107276
    [Google Scholar]
  38. Hao J. Dai X. Gao J. Li Y. Hou Z. Chang Z. Wang Y. Curcumin suppresses colorectal tumorigenesis via the Wnt/β-catenin signaling pathway by downregulating Axin2. Oncol. Lett. 2021 21 3 186 10.3892/ol.2021.12447 33574925
    [Google Scholar]
  39. van Loo G. Bertrand M.J.M. Death by TNF: A road to inflammation. Nat. Rev. Immunol. 2023 23 5 289 303 10.1038/s41577‑022‑00792‑3 36380021
    [Google Scholar]
  40. Tian S. Liao L. Zhou Q. Huang X. Zheng P. Guo Y. Deng T. Tian X. Curcumin inhibits the growth of liver cancer by impairing myeloid-derived suppressor cells in murine tumor tissues. Oncol. Lett. 2021 21 4 286 10.3892/ol.2021.12547 33732362
    [Google Scholar]
  41. Mohankumar K. Francis A.P. Pajaniradje S. Rajagopalan R. Synthetic curcumin analog: Inhibiting the invasion, angiogenesis, and metastasis in human laryngeal carcinoma cells via NF-kB pathway. Mol. Biol. Rep. 2021 48 8 6065 6074 10.1007/s11033‑021‑06610‑8 34355287
    [Google Scholar]
  42. Pandya N. Khan E. Jain N. Satham L. Singh R. Makde R.D. Mishra A. Kumar A. Curcumin analogs exhibit anti-cancer activity by selectively targeting G-quadruplex forming c-myc promoter sequence. Biochimie 2021 180 205 221 10.1016/j.biochi.2020.11.006 33188859
    [Google Scholar]
  43. Marcu K.B. Bossone S.A. Patel A.J. myc FUNCTION AND REGULATION. Annu. Rev. Biochem. 1992 61 1 809 858 10.1146/annurev.bi.61.070192.004113 1497324
    [Google Scholar]
  44. Jing Z. Liu Q. He X. Jia Z. Xu Z. Yang B. Liu P. NCAPD3 enhances Warburg effect through c-myc and E2F1 and promotes the occurrence and progression of colorectal cancer. J. Exp. Clin. Cancer. Res. 2022 41 1 198 10.1186/s13046‑022‑02412‑3 35689245
    [Google Scholar]
  45. Chen F.W. Wu Y.L. Cheng C.C. Hsiao Y.W. Chi J.Y. Hung L.Y. Chang C.P. Lai M.D. Wang J.M. Inactivation of pentraxin 3 suppresses M2-like macrophage activity and immunosuppression in colon cancer. J. Biomed. Sci. 2024 31 1 10 10.1186/s12929‑023‑00991‑7 38243273
    [Google Scholar]
  46. Oh J. An H.J. Kim J.O. Jun H.H. Kim W.R. Kim E.J. Oh D. Kim J.W. Kim N.K. Association between five common plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms and colorectal cancer susceptibility. Int. J. Mol. Sci. 2020 21 12 4334 10.3390/ijms21124334 32570732
    [Google Scholar]
  47. Jin X.S. Chen L.X. Ji T.T. Li R.Z. SERPINH1 promoted the proliferation and metastasis of colorectal cancer by activating PI3K/Akt/mTOR signaling pathway. World. J. Gastrointest. Oncol. 2024 16 5 1890 1907 10.4251/wjgo.v16.i5.1890 38764814
    [Google Scholar]
  48. Wang B. Gu B. Zhang T. Li X. Wang N. Ma C. Xiang L. Wang Y. Gao L. Yu Y. Song K. He P. Wang Y. Zhu J. Chen H. Good or bad: Paradox of plasminogen activator inhibitor 1 (PAI-1) in digestive system tumors. Cancer. Lett. 2023 559 216117 10.1016/j.canlet.2023.216117 36889376
    [Google Scholar]
  49. Kahles F. Findeisen H.M. Bruemmer D. Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes. Mol. Metab. 2014 3 4 384 393 10.1016/j.molmet.2014.03.004 24944898
    [Google Scholar]
  50. Amilca-Seba K. Tan T.Z. Thiery J.P. Louadj L. Thouroude S. Bouygues A. Sabbah M. Larsen A.K. Denis J.A. Osteopontin (OPN/SPP1), a mediator of tumor progression, is regulated by the mesenchymal transcription factor Slug/SNAI2 in colorectal cancer (CRC). Cells 2022 11 11 1808 10.3390/cells11111808 35681502
    [Google Scholar]
  51. Klement J.D. Poschel D.B. Lu C. Merting A.D. Yang D. Redd P.S. Liu K. Osteopontin blockade immunotherapy increases cytotoxic T lymphocyte lytic activity and suppresses colon tumor progression. Cancers 2021 13 5 1006 10.3390/cancers13051006 33670921
    [Google Scholar]
  52. Wei J.X. Luo Y. Xu Y. Xiao J.H. Osteoinductive activity of bisdemethoxycurcumin and its synergistic protective effect with human amniotic mesenchymal stem cells against ovariectomy-induced osteoporosis mouse model. Biomed. Pharmacother. 2022 146 112605 10.1016/j.biopha.2021.112605 35062070
    [Google Scholar]
  53. Lin Y.W. Weng X.F. Huang B.L. Guo H.P. Xu Y.W. Peng Y.H. IGFBP-1 in cancer: Expression, molecular mechanisms, and potential clinical implications. Am. J. Transl. Res. 2021 13 3 813 832 33841624
    [Google Scholar]
  54. Liu Y. Shen S. Yan Z. Yan L. Ding H. Wang A. Xu Q. Sun L. Yuan Y. Expression characteristics and their functional role of IGFBP gene family in pan-cancer. BMC Cancer 2023 23 1 371 10.1186/s12885‑023‑10832‑3 37088808
    [Google Scholar]
  55. Gligorijević N. Dobrijević Z. Šunderić M. Robajac D. Četić D. Penezić A. Miljuš G. Nedić O. The insulin-like growth factor system and colorectal cancer. Life 2022 12 8 1274 10.3390/life12081274 36013453
    [Google Scholar]
  56. Huang B.L. Wei L.F. Lin Y.W. Huang L.S. Qu Q.Q. Li X.H. Chu L.Y. Xu Y.W. Wang W.D. Peng Y.H. Wu F.C. Serum IGFBP-1 as a promising diagnostic and prognostic biomarker for colorectal cancer. Sci. Rep. 2024 14 1 1839 10.1038/s41598‑024‑52220‑2 38246959
    [Google Scholar]
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Antitumor and Immunoregulatory Effects of Curcumin Analog, (Z)-3-Hydroxy-1-(2-hydroxyphenyl)-3-phenyl prop-2-ene-1-one (DK1), on CT26-Tumor-Bearing BALB/c Mice
Bentham Science Publishers ; https://doi.org/10.2174/0109298673396217251003070048
/content/journals/cmc/10.2174/0109298673396217251003070048
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  • Article Type:     Research Article
Keywords: bovine serum ; BALB/c mice ; Curcumin analog ; anti-inflammatory ; immunophenotyping ; anticancer

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