CHEMOTHERAPEUTIC POTENTIAL OF NOVEL XANTHONE SOURCED FROM SWERTIA CHIRATA AGAINST SKIN CARCINOGENESIS

  • ATISH BARUA Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, West Bengal.
  • PRITHA CHOUDHURY Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, West Bengal.
  • CHINMAY KUMAR PANDA Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, West Bengal.
  • PROSENJIT SAHA Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, West Bengal.

Abstract

Objective: Swertia chirata forms a rich source of bio-active compounds, among which xanthones form an important part. Among the xanthones present in it, 1,5,8 Tri-hydroxy-3-methoxy xanthone (TMX) was found to be the most active. The present study aims to evaluate the chemotherapeutic potential of it against metastatic skin cancer cell lines.


Methods: In this study, the antitumor activity of TMX (the active component of chirata plant) was evaluated in A431, SKMEL-5, and A375 cell line by using in-vitro assays such as cell viability assay, cell cycle analysis, caspase 3 activity assay, intracellular reactive oxygen species (ROS) level determination by dichlorofluorescein diacetate, and quantitative real-time polymerase chain reaction (qRT-PCR).


Results: In vitro studies showed that TMX from S. chirata exhibited significant antitumor activity by inducing apoptosis and restricting proliferation in both melanoma and non-melanoma skin cancer cell lines, but no such activity was seen in normal skin cancer cell line WS1. The qRT-PCR analysis revealed that in both the melanoma ad non-melanoma cell lines, TMX could exert its antitumor activity by downregulating c-Myc, cyclin-D1, and β-catenin and up-regulating Wnt antagonist gsk-3β, thereby suppressing wnt self-renewal pathway, but such regulation was absent in normal cell line.


Conclusions: TMX from chirata could effectively inhibit the proliferation of metastatic skin cancer (both melanoma and non-melanoma) cell lines while being non-toxic to normal cell lines. The chemotherapeutic potential of TMX against metastatic skin cancer cell lines was achieved by downregulating several key regulatory genes enabling the suppression of the self-renewal pathway, the chief reason behind the invasiveness of cancer cells.

Keywords: Chirata, Metastasis, Melanoma, Squamous cell carcinoma, Xanthones

References

1. Seth D, Cheldize K, Brown D, Freeman EF. Global burden of skin disease: Inequities and innovations. Curr Dermatol Rep 2017;6:204-10.
2. Gamba CS, Clarke CA, Keegan TH, Tao L, Swetter SM. Melanoma survival disadvantage in young, non-Hispanic white males compared with females. JAMA Dermatol 2013;149:912-20.
3. Wehner MR, Serrano WC, Nosrati A, Schoen PM, Chren MM, Boscardin J, et al. All-cause mortality in patients with basal and squamous cell carcinoma: A systematic review and meta-analysis. J Am Acad Dermatol 2018;78:663-72.e3.
4. Gao SS, Yang XH, Wang M. Inhibitory effects of Bcell translocation gene 2 on skin cancer cells via the Wnt/?catenin signaling pathway. Mol Med Rep 2016;14:3464-8.
5. Shang S, Hua F, Hu ZW. The regulation of ?-catenin activity and function in cancer: Therapeutic opportunities. Oncotarget 2017;8:33972-89.
6. Torquato HF, Goettert MI, Justo GZ, Paredes-Gamero EJ. Anti-cancer phytometabolites targeting cancer stem cells. Curr Genomics 2017;18:156-74.
7. Kumar V, Van Staden J. A review of Swertia chirayita (Gentianaceae) as a traditional medicinal plant. Front Pharmacol 2016;6:308.
8. Fang CY, Wu CC, Fang CL, Chen WY, Chen CL. Long-term growth comparison studies of FBS and FBS alternatives in six head and neck cell lines. PLoS One 2017;12:e0178960.
9. Mohammadian M, Feizollahzadeh S, Mahmoudi R, Milani AT, Rezapour-Firouzi S, Douna BK. Hsp90 inhibitor; NVP-AUY922 in combination with doxorubicin induces apoptosis and downregulates VEGF in MCF-7 breast cancer cell line. Asian Pac J Cancer Prev 2020;21:1773-8.
10. Barua A, Choudhury P, Maity JK, Mandal SB, Mandal S, Saha P. Chemotherapeutic potential of novel non-toxic nucleoside analogues on EAC ascitic tumour cells. Free Radic Res 2019;53:57-67.
11. Ernst O, Zor T. Linearization of the Bradford protein assay. J Vis Exp 2010;38:1918.
12. Yamamoto T, Lewis J, Wataha J, Dickinson D, Singh B, Bollag WB, et al. Roles of catalase and hydrogen peroxide in green tea polyphenol-induced chemopreventive effects. J Pharmacol Exp Ther 2004;308:317-23.
13. Schneeberger C, Speiser P, Kury F, Zeillinger R. Quantitative detection of reverse transcriptase-PCR products by means of a novel and sensitive DNA stain. PCR Methods Appl 1995;4:234-8.
14. Shiozawa Y, Nie B, Pienta KJ, Morgan TM, Taichman RS. Cancer stem cells and their role in metastasis. Pharmacol Ther 2013;138:285-93.
15. Phi LT, Sari IN, Yang YG, Lee SH, Jun N, Kim KS, et al. Cancer stem cells (CSCs) in drug resistance and their therapeutic implications in cancer treatment. Stem Cells Int 2018;2018:5416923.
16. Lichota A, Gwozdzinski K. Anticancer activity of natural compounds from plant and marine environment. Int J Mol Sci 2018;19:3533.
17. Mousa HA. The potential modulatory effect of rutin on titanium dioxide nanoparticles-induced renal injury in male mice. Int J Pharm Pharm Sci 2020;2020:17-21.
18. Arumugam A, Wong NK. Comparison study of antioxidant, antimicrobial and cytotoxic properties of secondary metabolite and protein extracts from Clinacanthus nutans. Int J Pharm Pharm Sci 2020;2020:98-102.
19. Saikia T, Lalhlenmawia H, Laldinchhana, Roy PK, Thanzami K. Effect of polymeric nanoparticles of curcumin on a549 cell line. Int J Curr Pharm Res 2020;2020:50-3.
20. Greenwell M, Rahman PK. Medicinal plants: Their use in anticancer treatment. Int J Pharm Sci Res 2015;6:4103-12.
21. Frankfurt OS, Krishan A. Apoptosis-based drug screening and detection of selective toxicity to cancer cells. Anticancer Drugs 2003;14:555-61.
22. Wang X. Stem cells in tissues, organoids, and cancers. Cell Mol Life Sci 2019;76:4043-70.
23. Kovacs D, Migliano E, Muscardin L, Silipo V, Catricalà C, Picardo M, et al. The role of WNT/?-catenin signaling pathway in melanoma epithelial-to-mesenchymal-like switching: Evidences from patients-derived cell lines. Oncotarget 2016;7:43295-314.
24. Mohammed MK, Shao C, Wang J, Wei Q, Wang X, Collier Z, et al. Wnt/?-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance. Genes Dis 2016;3:11-40.
25. Barua A, Choudhury P, Mandal S, Panda CK, Saha P. Anti-metastatic potential of a novel xanthone sourced by Swertia chirata against in vivo and in vitro breast adenocarcinoma frameworks. Asian Pac J Cancer Prev 2020;21:2865-75.
Statistics
47 Views | 58 Downloads
Citations
How to Cite
BARUA, A., P. CHOUDHURY, C. K. PANDA, and P. SAHA. “CHEMOTHERAPEUTIC POTENTIAL OF NOVEL XANTHONE SOURCED FROM SWERTIA CHIRATA AGAINST SKIN CARCINOGENESIS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 13, no. 12, Dec. 2020, pp. 84-88, doi:10.22159/ajpcr.2020.v13i12.39842.
Section
Original Article(s)