Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis
Nada Abdullah,
Yahya Tamimi,
Sergey Dobretsov,
Najwa Al Balushi,
Jalila Alshekaili,
Hamed Al Balushi,
Mahmood Al Kindi,
Syed Imran Hassan,
Shadia Al Bahlani,
Benjamin K. Tsang,
Ikram A. Burney
Affiliations
Nada Abdullah
Department of Biochemistry, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, Oman
Yahya Tamimi
Department of Biochemistry, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, Oman
Sergey Dobretsov
Department of Marine Science & Fisheries, College of Agricultural & Marine Sciences, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, Oman
Najwa Al Balushi
Department of Biochemistry, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, Oman
Jalila Alshekaili
Department of Microbiology and Immunology, Sultan Qaboos University Hospital, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, Oman
Hamed Al Balushi
Department of Microbiology and Immunology, Sultan Qaboos University Hospital, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, Oman
Mahmood Al Kindi
Department of Microbiology and Immunology, Sultan Qaboos University Hospital, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, Oman
Syed Imran Hassan
Department of Chemistry, College of Science, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, Oman
Shadia Al Bahlani
Department of Allied Health Sciences, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, Oman
Benjamin K. Tsang
Departments of Obstetrics & Gynecology, Cellular & Molecular Medicine and the Interdisciplinary School of Health Sciences and the Centre for Infection, Immunity and Inflammation, Chronic Disease Program, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1N 6N5, Canada
Ikram A. Burney
Department of Medicine, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, Oman
High-grade epithelial ovarian cancer is a fatal disease in women frequently associated with drug resistance and poor outcomes. We previously demonstrated that a marine-derived compound MalforminA1 (MA1) was cytotoxic for the breast cancer cell line MCF-7. In this study, we aimed to examine the effect of MA1 on human ovarian cancer cells. The potential cytotoxicity of MA1was tested on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) ovarian cancer cell lines using AlamarBlue assay, Hoechst dye, flow cytometry, Western blot, and RT-qPCR. MA1 had higher cytotoxic activity on A2780S (IC50 = 0.23 µM) and A2780CP (IC50 = 0.34 µM) cell lines when compared to cisplatin (IC50 = 31.4 µM and 76.9 µM, respectively). Flow cytometry analysis confirmed the cytotoxic effect of MA1. The synergistic effect of the two drugs was obvious, since only 13% of A2780S and 7% of A2780CP cells remained alive after 24 h of treatment with both MA1 and cisplatin. Moreover, we examined the expression of bcl2, p53, caspase3/9 genes at RNA and protein levels using RT-qPCR and Western blot, respectively, to figure out the cell death mechanism induced by MA1. A significant down-regulation in bcl2 and p53 genes was observed in treated cells compared to non-treated cells (p < 0.05), suggesting that MA1 may not follow the canonical pathway to induce apoptosis in ovarian cancer cell lines. MalforminA1 showed promising anticancer activity by inducing cytotoxicity in cisplatin-sensitive and cisplatin-resistant cancer cell lines. Interestingly, a synergistic effect was observed when MA1 was combined with cisplatin, leading to it overcoming its resistance to cisplatin.
