Pyranocycloartobiloxanthone A Suppressed Metastasis Ovarian Cancer Cells via S Phase Cell Cycle Arrest and Apoptosis

Abd Rahman, Mashitoh and Hashim, Najihah Mohd and Ahmed, Idris Adewale (2023) Pyranocycloartobiloxanthone A Suppressed Metastasis Ovarian Cancer Cells via S Phase Cell Cycle Arrest and Apoptosis. Sains Malaysiana, 52 (12). pp. 3533-3550. ISSN 0126-6039, DOI https://doi.org/10.17576/jsm-2023-5212-15.

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Abstract

Ovarian cancer is a deadly disease with a poor prognosis, highlighting the urgent need for novel therapeutic alternatives. Pyranocycloartobiloxanthone A (PA), an exceptional xanthone compound has garnered attention due to its diverse medicinal properties. This study aimed to investigate the anticancer properties of PA on metastatic ovarian cancer SKOV-3 cells. Cytotoxicity was evaluated using an MTT assay, while apoptotic mechanisms were determined using AO/PI double staining, annexin V -fluorescein isothiocyanate, multiple cytotoxicity-3, reactive oxygen species (ROS) production, caspases, real-time PCR, western blot, human apoptosis protein profile array and cell cycle analysis. PA inhibited SKOV-3 cell proliferation in a time -dependent manner, with an IC50 of 7.0 +/- 0.5 mu g/mL and a selectivity index of 13.2 after 72 h of treatment. PA induced apoptosis through the intrinsic apoptotic pathway and arrested the cell cycle at the S phase. PA stimulated ROS production and disrupted the mitochondrial membrane potential, releasing cytochrome c from mitochondria to the cytosol. Additionally, results from human apoptotic protein profile indicated that 21 proteins were upregulated while 22 proteins were downregulated, including Bcl-2, survivin, and HSP70. These findings suggest that PA has the potential as a lead molecule in the development of a chemotherapy drug for ovarian cancer. However, further research is necessary to evaluate the safety and efficacy of PA in preclinical and clinical settings.

Item Type: Article
Funders: Universiti Malaya's Institute of Research Management and Monitoring for financial support (PPP-PG 022-2014 B) and the UMRG RP 001 C-13 BIO
Uncontrolled Keywords: Apoptosis; Artocarpus obtusus; cell cycle; ovarian cancer; pyranocycloartobiloxanthone A
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Divisions: Centre for Natural Products Research and Drug Discovery (CENAR)
Faculty of Pharmacy > Department of Pharmaceutical Chemistry
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 28 Oct 2025 08:17
Last Modified: 28 Oct 2025 08:17
URI: http://eprints.um.edu.my/id/eprint/50083

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