Experimental and computational evidence for xanthatin as a multi-target anti-cancer agent in ovarian cancer
DOI:
https://doi.org/10.3329/bjp.v20i4.84621Keywords:
Anti-cancer, Ovarian cancer, XanthatinAbstract
Xanthatin, a sesquiterpene lactone, was evaluated for its anti-cancer potential against SK-OV-3 ovarian cancer cells using both in vitro and in silico approaches. In vitro, xanthatin reduced cell viability, induced lactate dehydrogenase release, increased intracellular reactive oxygen species, and inhibited cell migration. The loss of mitochondrial mem-brane potential, activation of caspase-3 and caspase-9, and altered expression of BAX, CASPASE-3, and BCL-2 confirmed the induction of apoptosis. SwissADME and ProTox-II predicted favorable pharmacokinetic properties and safety profiles. Molecular docking suggested multi-target binding to tubulin, STAT3, VEGFR2, and topoisomerase II. These findings indicate that xanthatin exerts cytotoxic, pro-apoptotic, and anti-migratory effects by inducing oxidative stress and mitochondrial dysfunction. Therefore, xanthatin may represent a promising natural product lead for ovarian cancer therapy.
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References
Alalawy AI. Key genes and molecular mechanisms related to paclitaxel resistance. Cancer Cell Int. 2024; 24: 244.
Alrosan K, Alrosan AZ, Heilat GB, Alrousan AF, Gammoh OS, Alqudah A, Madaeen S, Alrousan MJ. Treatment of ovarian cancer: From the past to the new era. Oncol Lett. 2025; 30: 384.
Arshad H, Saleem M. Cytotoxic effect of Luffa cylindrica leaf extract on MCF-7 cell lines. Bangladesh J Pharmacol. 2025; 20: 101-12.
Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: A webserver for prediction of toxicity of chemicals. Nucleic Acids Res. 2018; 46: W257-63.
Biovia. Discovery Studio Visualizer: User guide. San Diego, CA, Dassault Systèmes BIOVIA, 2021.
BioVision, Inc. Caspase-3 colorimetric assay kit and caspase-9 colorimetric assay kit: Protocols. Milpitas, CA, BioVision, Inc., 2022.
Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT. The MIQE guidelines: Minimum information for publication of qPCR experiments. Clin Chem. 2009; 55: 611-22.
Bustin SA, Garson JA, Coward A. The dMIQE guidelines update: Minimum information for digital PCR. Clin Chem. 2020; 66: 1012-29.
Bustin S, Huggett J. qPCR primer design revisited. Biomol Detect Quantif. 2017; 14: 19-28.
Chen H, Zhu T, Huang X, Xu W, Di Z, Ma Y, Xue M, Bi S, Shen Y, Yu Y, Shen Y, Feng L. Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K‐Akt–mTOR pathway. Pharmacol Res Perspect. 2023; 11: e01041.
Chuwa AH, Mvunta DH. Prognostic and clinicopathological significance of surviving in endometrial and ovarian cancers. Oncol Rev. 2024; 13: 1444008.
Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017; 7: 42717.
Daina A, Michielin O, Zoete V. SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019; 47: W357-64.
Eberhardt J, Santos-Martins D, Tillack AF, Forli S. AutoDock Vina 1.2.0: New docking methods and expanded force field. JCIM. 2021; 61: 3891-98.
Frąszczak K, Barczynski B. The role of cancer stem cell markers in ovarian cancer. Cancers (Basel). 2024; 16: 40.
Gao X, Li Y, Xu H, Ni S, Pan H, Ma C, Zhao X, Zhang H. Xanthatin induces apoptosis through ROS-mediated c-FLIP inhibition in human retinoblastoma cells. Front Med. 2025; 12: 1554934.
Geng Y, Liu P, Xie Y, Liu Y, Zhang X, Hou X, Zhang L. Xan-thatin suppresses pancreatic cancer cell growth via the ROS/RBL1 signaling pathway: In vitro and in vivo insights. Phytomedicine 2023; 119: 155004.
Grada A, Otero-Vinas M, Prieto-Castrillo F, Obagi Z, Falanga V. Research techniques made simple: analysis of collective cell migration using the wound healing assay. J Invest Dermatol. 2017; 137: e11-16.
Grillo E, Romani C, Ettorre VM, Santin AD, Mitola S. The VEGF/VEGFR2 system in ovarian cancer: From functional to pharmacological significance. Biochim Biophys Acta Rev Cancer. 2025; 189374.
He Y, Sun MM, Zhang GG, Yang J, Chen KS, Xu WW, Li B. Targeting PI3K/AKT signal transduction for cancer therapy. Signal Transduct Target Ther. 2021; 6: 425.
Hsu CY, Rajabi S, Hamzeloo-Moghadam M, Kumar A, Maresca M, Ghildiyal P. Sesquiterpene lactones as emerging biomolecules to cease cancer by targeting apoptosis. Front Pharmacol. 2024; 15: 1371002.
Izycka N, Rucinski M, Andrzejewska M, Szubert S, Nowak-Markwitz E, Sterzynska K. The prognostic value of cancer stem cell markers (CSCs) expression—ALDH1A1, CD133, CD44—for survival and long-term follow-up of ovarian cancer patients. Prognostic value of ALDH1A1, CD133, CD44 in ovarian cancer. Int J Mol Sci. 2023; 24: 2400.
Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, Li Q, Shoemaker BA, Thiessen PA, Yu B, Zaslavsky L, Zhang J, Bolton EE. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res. 2021; 49: D1388-95.
Lee E, Yang D, Hong JH. Prominent naturally derived oxidative-stress-targeting drugs and their applications in cancer treatment. Antioxidants. 2025; 14: 49.
Liang CC, Park AY, Guan JL. In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007; 2: 329-33.
Liang ST, Chen C, Chen RX, Li R, Chen WL, Jiang GH, Du LL. Michael acceptor molecules in natural products and their mechanism of action. Front Pharmacol. 2022; 13: 1033003
Liu Y, Zhang X, Cheng F, Cao W, Geng Y, Chen Z, Wei W, Zhang L. Xanthatin induce DDP-resistance lung cancer cells apoptosis through regulation of GLUT1 mediated ROS accumulation. Drug Dev Res. 2023; 84: 1266-78.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 2001; 25: 402-08.
Malekzadeh R, Arjmand M, Akbari Z, Sadeghi S, Hosseini RH. The effect of Xanthium strumarium root extracts on growth inhibition of epithelial ovarian cancer SK-OV-3 cell line: A metabolomics-based study. Jundishapur J Nat Pharm Prod. 2023; 18.
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem. 2009; 30: 2785-91.
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera: Visualization system for research and analysis. J Comput Chem. 2004; 25: 1605-12.
Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez JY. Fiji: An open-source platform for biological-image analysis. Nat Methods. 2012; 9: 676-82.
Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012; 9: 671-75.
Thermo Fisher Scientific. Pierce BCA protein assay kit: User guide. Rockford, IL, Thermo Fisher Scientific, 2022.
Tia ST, Luo M, Fan W. Mapping the role of P-gp in multidrug resistance: Insights from recent structural studies. Int J Mol Sci. 2025; 26: 4179.
Tossetta G, Fantone S, Montanari E, Marzioni D, Goteri G. Role of NRF2 in ovarian cancer. Antioxidants 2022; 11: 663.
van Meerloo J, Kaspers GJ, Cloos J. Cell sensitivity assays: The MTT assay. In: Cancer cell culture: Methods and protocols. Totowa, Humana Press, 2011, pp. 237-45.
Wang L, Wang X, Zhu X, Zhong L, Jiang Q, Wang Y. Drug resistance in ovarian cancer: From mechanism to clinical application. Mol Cancer. 2024; 23: 66.
Wordeman L, Vicente JJ. Microtubule targeting agents in disease: Classic drugs, novel roles. Cancers 2021; 13: 5650.
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