Skip to content
2000
image of Laccaic Acid A: A Natural Anthraquinone with Potent Anticancer Activity against MDA-MB-231 Cells

Abstract

Background/Aim

This study aims to isolate and evaluate the anticancer potential of laccaic acids from lac dye by utilizing polarity-based fractionation and high-performance liquid chromatography (HPLC).

Methods

In this study, polarity-based fractionation of lac dye was performed to isolate its constituents. A novel HPLC method was developed for the chromatographic separation of lac dye components, utilizing gradient elution with two solvents: 0.1% (v/v) formic acid in LCMS-grade water (A) and 90:10 acetonitrile HPLC-grade (B) at a flow rate of 0.4 mL/min. This method facilitated the isolation of four key constituents: laccaic acid D, laccaic acid B, laccaic acid C, and laccaic acid A.

Results

The purity of these compounds was confirmed LCMS methods. The anticancer activity of the isolated constituents was evaluated against the MDA-MB-231 cell line using the MTT assay. Notably, laccaic acid A demonstrated significant anticancer activity with an IC value of less than 100 nM, comparable to that of Adriamycin. Further investigations into the apoptotic activity of laccaic acid A were conducted using flow cytometry, revealing that laccaic acid A is a non-necrotic and apoptotic inducer. Additionally, considering that an effective anticancer agent may also exhibit antioxidant, anti-inflammatory, and anti-angiogenesis properties, the isolated laccaic acids were accessed for these biological activities.

Conclusion

The results were promising, indicating that laccaic acids could offer a multifaceted approach to cancer treatment. This study highlights the potential of laccaic acids as valuable candidates for anticancer therapy and warrants further investigation into their mechanisms of action and therapeutic efficacy.

Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266338478250314231400
2025-04-04
2025-09-13
Loading full text...

Full text loading...

References

  1. Lozano R. Naghavi M. Foreman K. Lim S. Shibuya K. Aboyans V. Abraham J. Adair T. Aggarwal R. Ahn S.Y. AlMazroa M.A. Alvarado M. Anderson H.R. Anderson L.M. Andrews K.G. Atkinson C. Baddour L.M. Barker-Collo S. Bartels D.H. Bell M.L. Benjamin E.J. Bennett D. Bhalla K. Bikbov B. Abdulhak A.B. Birbeck G. Blyth F. Bolliger I. Boufous S. Bucello C. Burch M. Burney P. Carapetis J. Chen H. 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. Dahodwala N. De Leo D. Degenhardt L. Delossantos A. Denenberg J. Des Jarlais D.C. Dharmaratne S.D. Dorsey E.R. Driscoll T. Duber H. Ebel B. Erwin P.J. Espindola P. Ezzati M. Feigin V. Flaxman A.D. Forouzanfar M.H. Fowkes F.G.R. Franklin R. Fransen M. Freeman M.K. Gabriel S.E. Gakidou E. Gaspari F. Gillum R.F. Gonzalez-Medina D. Halasa Y.A. Haring D. Harrison J.E. Havmoeller R. Hay R.J. Hoen B. Hotez P.J. Hoy D. Jacobsen K.H. James S.L. Jasrasaria R. Jayaraman S. Johns N. Karthikeyan G. Kassebaum N. Keren A. Khoo J-P. Knowlton L.M. Kobusingye O. Koranteng A. Krishnamurthi R. Lipnick M. Lipshultz S.E. Ohno S.L. Mabweijano J. MacIntyre M.F. Mallinger L. March L. Marks G.B. Marks R. Matsumori A. Matzopoulos R. Mayosi B.M. McAnulty J.H. McDermott M.M. McGrath J. Memish Z.A. Mensah G.A. Merriman T.R. Michaud C. Miller M. Miller T.R. Mock C. Mocumbi A.O. Mokdad A.A. Moran A. Mulholland K. Nair M.N. Naldi L. Narayan K.M.V. Nasseri K. Norman P. O’Donnell M. Omer S.B. Ortblad K. Osborne R. Ozgediz D. Pahari B. Pandian J.D. Rivero A.P. Padilla R.P. Perez-Ruiz F. Perico N. Phillips D. Pierce K. Pope C.A. III Porrini E. Pourmalek F. Raju M. Ranganathan D. Rehm J.T. Rein D.B. Remuzzi G. Rivara F.P. Roberts T. De León F.R. Rosenfeld L.C. Rushton L. Sacco R.L. Salomon J.A. Sampson U. Sanman E. Schwebel D.C. Segui-Gomez M. Shepard D.S. Singh D. Singleton J. Sliwa K. Smith E. Steer A. Taylor J.A. Thomas B. Tleyjeh I.M. Towbin J.A. Truelsen T. Undurraga E.A. Venketasubramanian N. Vijayakumar L. Vos T. Wagner G.R. Wang M. Wang W. Watt K. Weinstock M.A. Weintraub R. Wilkinson J.D. Woolf A.D. Wulf S. Yeh P-H. Yip P. Zabetian A. Zheng Z-J. Lopez A.D. Murray C.J.L. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012 380 9859 2095 2128 10.1016/S0140‑6736(12)61728‑0 23245604
    [Google Scholar]
  2. Media Centre, WHO – 2024. Available from: https://www.emro.who.int/media/news/world-cancer-day-2024.html Last Accessed on 18 June 2024.
  3. Wang X. Li J. Fan Y. Jin X. Present research on the composition and application of lac. For. Stud. China 2006 8 1 65 69 10.1007/s11632‑006‑0012‑9
    [Google Scholar]
  4. Anitha S.S. Pharmacological activity of vinca alkaloids. J. Pharmacogn. Phytochem. 2016 4 27 34
    [Google Scholar]
  5. Hirata K. Uematsu Y. Suzuki K. Iida K. Yasuda K. Saito K. Analysis of main pigments and other ingredients in lac color product. Shokuhin Eiseigaku Zasshi 2001 42 2 109 113 10.3358/shokueishi.42.109 11486376
    [Google Scholar]
  6. Kalantari S. Roufegarinejad L. Pirsa S. Gharekhani M. Green extraction of bioactive compounds of pomegranate peel using β-Cyclodextrin and ultrasound. Main Group Chemistry 2020 19 1 61 80 10.3233/MGC‑190821
    [Google Scholar]
  7. Dey S. Ghosh M. An anticancer agent from lacciferlacca (Kerr): Laccaic acid-A. Indian J. Tradit. Knowl. 2019 18 4 677 685
    [Google Scholar]
  8. Mehandale A.R. Rao A.V.R. Shaikh I.N. Venkataraman K. Desoxyerythrolaccin and laccaic acid D. Tetrahedron Lett. 1968 9 18 2231 2234 10.1016/S0040‑4039(00)89727‑0
    [Google Scholar]
  9. Fagan R.L. Cryderman D.E. Kopelovich L. Wallrath L.L. Brenner C. Laccaic acid A is a direct, DNA-competitive inhibitor of DNA methyltransferase 1. J. Biol. Chem. 2013 288 33 23858 23867 10.1074/jbc.M113.480517 23839987
    [Google Scholar]
  10. Jimtaisong A. Janthadee R. Nakrit T. In vitro antioxidant activities of laccaic acids and its aluminum lake. Food Sci. Biotechnol. 2013 22 4 1055 1061 10.1007/s10068‑013‑0183‑9
    [Google Scholar]
  11. Sekido C. Nishimura N. Takai M. Hasumi K. Inhibition of plasma hyaluronan-binding protein autoactivation by laccaic acid. Biosci. Biotechnol. Biochem. 2010 74 11 2320 2322 10.1271/bbb.100373 21071862
    [Google Scholar]
  12. Burwood R. Read G. Schofield K. Wright D.E. 1133. The pigments of stick lac. Part I. Isolation and preliminary examination. J. Chem. Soc. 1965 6067 6073 10.1039/jr9650006067
    [Google Scholar]
  13. Burwood R. Read G. Schofield K. Wright D.E. The pigments of stick lac. Part II. The structure of laccaic acid A. J. Chem. Soc. C 1967 842 851 10.1039/j39670000842
    [Google Scholar]
  14. Bhide N.S. Pandhare E.D. Rama Rao A.V. Shaikh I.N. Srini- vasan, R. Lac pigments: Part IV. Constitution of laccaic acid B. Indian J. Chem. 1969 7 10 987 995
    [Google Scholar]
  15. Oka H. Ito Y. Yamada S. Kagami T. Hayakawa J. Harada K. Atsumi E. Suzuki M. Suzuki M. Odani H. Akahori S. Maeda K. Nakazawa H. Ito Y. Separation of lac dye components by high-speed counter-current chromatography. J. Chromatogr. A 1998 813 1 71 77 10.1016/S0021‑9673(98)00311‑2 9697316
    [Google Scholar]
  16. Oka H. Ito Y. Yamada S. Kagami T. Hayakawa J. Harada K. Atsumi E. Suzuki M. Suzuki M. Odani H. Akahori S. Maeda K. Tanaka T. Mizuno M. Identification of lac dye com- ponents by electrospray high performance liquid chromatography- tandem mass spectrometry. J. Mass Spectrom. Soc. Jpn. 1998 46 1 63 68 10.5702/massspec.46.63
    [Google Scholar]
  17. Hirata K. Uematsu Y. Suzuki K. Iida K. Kamata K. Analysis of lac color in diets and feces of rats for toxicity studies. Shokuhin Eiseigaku Zasshi 2002 43 2 110 113 10.3358/shokueishi.43.110 12092412
    [Google Scholar]
  18. Skehan P. Storeng R. Scudiero D. Monks A. McMahon J. Vistica D. Warren J.T. Bokesch H. Kenney S. Boyd M.R. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst. 1990 82 13 1107 1112 10.1093/jnci/82.13.1107 2359136
    [Google Scholar]
  19. Dagur P. Ghosh M. Evaluation of antiproliferative activity of lac dye fractions against MDA-MB-231 and SiHa cell lines. Anticancer. Agents Med. Chem. 2022 22 14 2577 2585 10.2174/1872210516666220224095221 35209821
    [Google Scholar]
  20. Dey S. Ghosh M. A LC/MS-MS guided isolation of laccaic acid-A: A potent antimicrobial agent. Indian Journal of Pharmaceutical Education and Research 2018 52 4s Suppl. 2 S287 S295 10.5530/ijper.52.4s.109
    [Google Scholar]
  21. Chaube U.J. Rawal R. Jha A.B. Variya B. Bhatt H.G. Design and development of Tetrahydro-Quinoline derivatives as dual mTOR-C1/C2 inhibitors for the treatment of lung cancer. Bioorg. Chem. 2021 106 104501 10.1016/j.bioorg.2020.104501 33280832
    [Google Scholar]
  22. Sharma N. Samarakoon K. Gyawali R. Park Y.H. Lee S.J. Oh S. Lee T.H. Jeong D. Evaluation of the antioxidant, anti-inflammatory, and anticancer activities of Euphorbia hirta ethanolic extract. Molecules 2014 19 9 14567 14581 10.3390/molecules190914567 25225720
    [Google Scholar]
  23. Nanjo F. Goto K. Seto R. Suzuki M. Sakai M. Hara Y. Scavenging effects of tea catechins and their derivatives on 1,1-diphenyl-2-picrylhydrazyl radical. Free Radic. Biol. Med. 1996 21 6 895 902 10.1016/0891‑5849(96)00237‑7 8902534
    [Google Scholar]
  24. Rajan T.S. Giacoppo S. Iori R. De Nicola G.R. Grassi G. Pollastro F. Bramanti P. Mazzon E. Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages. Fitoterapia 2016 112 104 115 10.1016/j.fitote.2016.05.008 27215129
    [Google Scholar]
  25. Hur S.J. Choi S.Y. Lim B.O. In vitro anti-inflammatory activity of Russula virescens in the macrophage like cell line RAW 264.7 activated by lipopolysaccharide. J. Nutr. Food Sci. 2012 2 4 10.4172/2155‑9600.1000142
    [Google Scholar]
  26. Re R. Pellegrini N. Proteggente A. Pannala A. Yang M. Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med. 1999 26 9-10 1231 1237 10.1016/S0891‑5849(98)00315‑3 10381194
    [Google Scholar]
  27. Ilyasov I.R. Beloborodov V.L. Selivanova I.A. Terekhov R.P. ABTS/PP decolorization assay of antioxidant capacity reaction pathways. Int. J. Mol. Sci. 2020 21 3 1131 10.3390/ijms21031131 32046308
    [Google Scholar]
  28. D’Arcy P.F. Howard E.M. A new anti-inflammatory test, utilizing the chorio-allantoic membrane of the chick embryo. Br. J. Pharmacol. Chemother. 1967 29 3 378 387 10.1111/j.1476‑5381.1967.tb01969.x 6034385
    [Google Scholar]
  29. Marchesan M. Paper D.H. Hose S. Franz G. Investigation of the antiinflammatory activity of liquid extracts of Plantago lanceolata L. Phytother. Res. 1998 12 S1 S33 S34 10.1002/(SICI)1099‑1573(1998)12:1+<S33::AID‑PTR242>3.0.CO;2‑B
    [Google Scholar]
  30. Aidoo D.B. Konja D. Henneh I.T. Ekor M. Protective effect of bergapten against human erythrocyte hemolysis and protein denaturation in vitro. Int. J. Inflamm. 2021 2021 1 7 10.1155/2021/1279359 34970434
    [Google Scholar]
  31. Lokman N.A. Elder A.S.F. Ricciardelli C. Oehler M.K. Chick chorioallantoic membrane (CAM) assay as an in vivo model to study the effect of newly identified molecules on ovarian cancer invasion and metastasis. Int. J. Mol. Sci. 2012 13 8 9959 9970 10.3390/ijms13089959 22949841
    [Google Scholar]
  32. Li M. Pathak R.R. Lopez-Rivera E. Friedman S.L. Aguirre-Ghiso J.A. Sikora A.G. The <em>In Ovo </em>Chick Chorioallantoic Membrane (CAM) assay as an efficient xenograft model of hepatocellular carcinoma. J. Vis. Exp. 2015 52411 104 10.3791/52411‑v 26484588
    [Google Scholar]
  33. Dey R. Shaw S. Bhatt H. Patel B. Yadav R. Chaube U. Synthesis, biological screening, and binding mode analysis of some N-substituted tetrahydroquinoline analogs as apoptosis inducers and anticancer agents. J. Mol. Struct. 2024 1318 1 139330 10.1016/j.molstruc.2024.139330
    [Google Scholar]
  34. Shaw S. Dey R. Bhatt H. Patel B. Patel S. Dixit N. Chaube U. Designing of target‐specific N ‐substituted tetrahydroquinoline derivatives as potent mTOR inhibitors via integrated structure‐guided computational approaches. ChemistrySelect 2024 9 7 e202303291 10.1002/slct.202303291
    [Google Scholar]
  35. Chaube U. Dey R. Shaw S. Patel B.D. Bhatt H.G. Tetrahydroquinoline: An efficient scaffold as mTOR inhibitor for the treatment of lung cancer. Future Med. Chem. 2022 14 23 1789 1809 10.4155/fmc‑2022‑0204 36538021
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266338478250314231400
Loading
/content/journals/ctmc/10.2174/0115680266338478250314231400
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keywords: Laccaic acids ; MTT assay ; DPPH assay ; cam assay ; cell apoptosis assay
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test