Antiproliferative activity and gas chromatography–tandem mass spectrometry profiling of Wrightia tinctoria bark fractions
Breast and prostate cancers contribute substantially to cancer-related morbidity and mortality. Despite significant advancements in cancer treatment modalities, there remains a need to deepen mechanistic understanding and develop improved therapeutic strategies, given toxicity, resistance, and limited selectivity. Natural products have played a pivotal role in drug discovery. The structural diversity of natural compounds allows them to target multiple pathways, making them promising candidates in anticancer drug development. Wrightia tinctoria (WT), widely used in Ayurvedic and traditional medicine, has emerged as a plant of significant pharmacological interest. The present study focuses on identifying the bioactive constituents of WT bark through bioassay-guided fractionation, chromatographic techniques, and mass spectrometric profiling. In the present study, polarity-based fractions, including petroleum ether, hexane, chloroform, ethyl acetate, and methanol, were screened for their antiproliferative effects against MDA-MB-231, MCF-7, and PC-3 cancer cell lines. Among these, the petroleum ether fraction (PFWT) showed potent cytotoxic activity, with IC50 values of 59.73 ± 2.90, 97.06 ± 4.76, and 43.63 ± 2.68 μg/mL, respectively. The gas chromatography–tandem mass spectrometry analysis of sub-fractions from PFWT further tentatively identified 42 chemical compounds, out of which 27 compounds are reported for the first time. Overall, the study demonstrates that PFWT possesses strong and broad antiproliferative activity, reinforcing the value of integrating traditional medicinal knowledge with modern analytical and pharmacological approaches. These findings position WT as a promising and sustainable source of novel anticancer agents and warrant further in-depth investigation.
- World Health Organization. Global cancer burden growing amidst mounting need for services. Published 2024. Available from: https://www.who.int/news/item/01-02- 2024-global-cancer-burden-growing--amidst-mounting-need-for-services [Last accessed on 2025 Nov 26].
- De Silva F, Alcorn J. A tale of two cancers: A current concise overview of breast and prostate cancer. Cancers. 2022;14(12):2954. doi: 10.3390/cancers14122954.
- Luo Q, Smith DP. Global cancer burden: progress, projections, and challenges. Lancet. 2025;406(10512):1536- 1537. doi: 10.1016/s0140-6736(25)01570-3
- Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2021;71(3):209-249. doi: 10.3322/caac.21660
- Zafar, A., Khatoon, S., Khan, M.J. et al. Advancements and limitations in traditional anti-cancer therapies: a comprehensive review of surgery, chemotherapy, radiation therapy, and hormonal therapy. Discov Onc. 2025;16:607. doi: 10.1007/s12672-025-02198-8
- Krzyszczyk P, Acevedo A, Davidoff EJ, et al. The growing role of precision and personalized medicine for cancer treatment. Technology. 2018;06(03n04):79-100. doi: 10.1142/s2339547818300020
- Mangani S, Piperigkou Z, Koletsis NE, Ioannou P, Karamanos NK. Estrogen receptors and extracellular matrix: the critical interplay in cancer development and progression. FEBS J. 2024;292(7):1558-1572. doi: 10.1111/febs.17270
- Harris R, Lohr K. Screening for prostate cancer: An update of the evidence for the U.S. Preventive Services Task Force. Ann Inter Med. 2002;137(11):917-929. doi: 10.7326/0003-4819-137-11-200212030-00014
- Barqawi AB, Krughoff KJ, Eid K. Current challenges in prostate cancer management and the rationale behind targeted focal therapy. Adv Urol. 2012;2012:862639. doi: 10.1155/2012/862639
- Abotaleb M, Kubatka P, Caprnda M, et al. Chemotherapeutic agents for the treatment of metastatic breast cancer: An update. Biomed Pharmacother. 2018;101:458-477. doi: 10.1016/j.biopha.2018.02.033
- Amjad MT, Chidharla A, Kasi A. Cancer Chemotherapy. Treasure Island (FL): StatPearls Publishing; 2025.
- Rojas A, González I, Morales MA. Natural products and cancer: The urgent need to bridge the gap between preclinical and clinical research. World J Gastrointest Oncol. 2025; Apr 15;17(4):100484. doi: 10.4251/wjgo.v17.i4.100484.
- Younes M, Loubnane G, Sleiman C, Rizk S. Tocotrienol isoforms: The molecular mechanisms underlying their effects in cancer therapy and their implementation in clinical trials. J Integr Med. 2024;22(1):1-11. doi: 10.1016/j.joim.2024.01.002
- Zhu LH, Liang YP, Yang L, Zhu F, Jia LJ, Li HG.Cycloastragenol induces apoptosis and protective autophagy through AMPK/ ULK1/mTOR axis in human non-small cell lung cancer cell lines. J Integr Med. 2024;22(4):503-514. doi: 10.1016/j.joim.2024.05.004
- Kanchi MM, Shanmugam MK, Rane G, Sethi G, Kumar AP. Tocotrienols: the unsaturated sidekick shifting new paradigms in vitamin E therapeutics. Drug Discov Today. 2017;22(12):1765-1781. doi: 10.1016/j.drudis.2017.08.001
- Kashyap D, Sharma A, Tuli HS, et al. Apigenin: A natural bioactive flavone-type molecule with promising therapeutic function. J Funct Foods. 2018;48:457-471. doi: 10.1016/j.jff.2018.07.037
- Ding Y, Peng Y, Deng L, Fan J, Huang B. Gamma-tocotrienol reverses multidrug resistance of breast cancer cells with a mechanism distinct from that of atorvastatin. J Steroid Biochem Mol Biol. 2017;167:67-77. doi: 10.1016/j.jsbmb.2016.11.009
- Moudi M, Go R, Yien CYS, Nazre M. Vinca alkaloids. Int J Prev Med. 2013;4:1231-1235.
- Basili S, Moro S. Novel camptothecin derivatives as topoisomerase I inhibitors. Expert Opin Ther Patents. 2009;19(4):555-574. doi: 10.1517/13543770902773437
- Chunarkar-Patil P, Kaleem M, Mishra R, et al. Anticancer drug discovery based on natural products: From computational approaches to clinical studies. Biomedicines. 2024;12(1):201. doi: 10.3390/biomedicines12010201
- Li Z, Chen K, Rose P, Zhu YZ. Natural products in drug discovery and development: Synthesis and medicinal perspective of leonurine. Front Chemistry. 2022;10:1036329. doi: 10.3389/fchem.2022.1036329
- Paul JK, Azmal M, Haque ASNB, Talukder OF, Meem M, Ghosh A. Phytochemical-mediated modulation of signaling pathways: A promising avenue for drug discovery. Adv Redox Res. 2024;13:100113. doi: 10.1016/j.arres.2024.100113
- George BP, Chandran R, Abrahamse H. Role of phytochemicals in cancer chemoprevention: Insights. Antioxidants. 2021;10(9):1455. doi: 10.3390/antiox10091455
- Raina R, Pramodh S, Rais N, et al. Luteolin inhibits proliferation, triggers apoptosis and modulates Akt/mTOR and MAP kinase pathways in HeLa cells. Oncol Lett. 2021;21(3). doi: 10.3892/ol.2021.12452
- Yang J, Sun Q, Liu X, et al. Targeting Notch signaling pathways with natural bioactive compounds: A promising approach against cancer. Front Pharmacol. 2024;15:1412669. doi: 10.3389/fphar.2024.1412669
- Kale N, et al. Phyto-pharmacological profile of Wrightia tinctoria. Phytother Res. 2021;35(1):301-308. doi: 10.52711/2231-5659.2021.00047
- Sirigireddy LD, Divakar M. Wrightia tinctoria (Roxb) R.Br. - An updated Review. HJDMed. 2014;6(1):95-105. doi: 10.15254/h.j.d.med.6.2014.126
- Rao B, Rajeswari D, Devarakonda R, Battu H. Phytochemical and pharmacological studies on Wrightia tinctoria. World J Pharm Pharm Sci. 2019.
- Fatima N, Ahmad MK, Ansari JA, et al. Anticancer, antioxidant potential and profiling of polyphenolic compounds of Wrightia tinctoria Roxb. (R. Br.) bark. J Adv Pharm Technol Res. 2016;7(4):159-165. doi: 10.4103/2231-4040.191428
- Alara OR, Abdurahman NH, Ukaegbu CI. Extraction of phenolic compounds: A review. Curr Res Food Sci. 2021;4:200-214. doi: 10.1016/j.crfs.2021.03.011
- Haghnavaz N, Asghari F, Elieh Ali Komi D, Shanehbandi D, Baradaran B, Kazemi T. HER2 positivity may confer resistance to therapy with paclitaxel in breast cancer cell lines. Artif Cells Nanomed Biotechnol. 2017;46(3):518-523. doi: 10.1080/21691401.2017.1326927
- Zhao Y, Zeng X, Tang H, Ye D, Liu J. Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria-dependent pathway. Oncol Lett. 2019 May;17(5):4277-4284. doi: 10.3892/ol.2019.10119
- Kaminsky R, Schmid C, Brun R. An in vitro selectivity index for evaluation of cytotoxicity of antitrypanosomal compounds. Vitro Toxicol. 1996;9:315-324.
- Sutejo IR, Putri H, Meiyanto E: The Selectivity of Ethanolic Extract of Buah Makassar (Brucea javanica) on Metastatic Breast Cancer Cells. J Agromed Med Sci. 2016;2(1):1. doi: 10.19184/ams.v2i1.2422
- Badisa RB, Darling-Reed SF, Joseph P, Cooperwood JS, Latinwo LM, Goodman CB. Selective cytotoxic activities of two novel synthetic drugs on human breast carcinoma MCF-7 cells. Anticancer Res. 2009;29:2993-2996.
- Thiagarajan MK, Chandrasekharan D, Mahalingam R, Ravi A. Evaluation of in vitro anti-cancer potential and apoptotic profile of ethanolic plant extract of Wrightia tinctoria against oral cancer cell line. J Oral Maxillofac Pathol. 2024;28(2):211- 215. doi: 10.4103/jomfp.jomfp_32_24
- Antony J, Saikia M, VV, et al. DW-F5: A novel formulation against malignant melanoma from Wrightia tinctoria. Sci Rep. 2015;5:11107. doi: 10.1038/srep11107
38 Najmi A, Javed SA, Al Bratty M, Alhazmi HA. Modern approaches in the discovery and development of plant-based natural products and their analogues as potential therapeutic agents. Molecules. 2022;27(2):349. doi: 10.3390/molecules27020349
- Ansari JA, Rastogi N, Ahmad MK, et al. ROS mediated pro-apoptotic effects of Tinospora cordifolia on breast cancer cells. Front Biosci. 2017;9:89-100. doi: 10.2741/e788
- Ansari JA, Ahmad MK, Khan AR, et al. Anticancer and antioxidant activity of Zingiber officinale Roscoe rhizome. Front Pharmacol. 2016;7:472. doi: 10.3389/fphar.2016.00472
- Chen L, Teng H, Xie Z, et al. Modifications of dietary flavonoids towards improved bioactivity: An update on structure–activity relationship. Crit Rev Food Sci Nutr. 2018;58(4):513-527. doi: 10.1080/10408398.2016.1196334
- Balunas MJ, Kinghorn AD. Drug discovery from medicinal plants. Life Sci. 2005;78(5):431-441. doi: 10.1016/j.lfs.2005.09.012
