Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis
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 effec...
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MDPI AG
2021-06-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Nada Abdullah |
| collection | DOAJ |
| description | 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 (<i>p</i> < 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. |
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| language | English |
| last_indexed | 2024-03-10T10:26:42Z |
| publishDate | 2021-06-01 |
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| spelling | doaj.art-ccc40e8fc48e454fb349d81253e0eba82023-11-21T23:58:50ZengMDPI AGMolecules1420-30492021-06-012612362410.3390/molecules26123624Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced ApoptosisNada Abdullah0Yahya Tamimi1Sergey Dobretsov2Najwa Al Balushi3Jalila Alshekaili4Hamed Al Balushi5Mahmood Al Kindi6Syed Imran Hassan7Shadia Al Bahlani8Benjamin K. Tsang9Ikram A. Burney10Department of Biochemistry, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, OmanDepartment of Biochemistry, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, OmanDepartment of Marine Science & Fisheries, College of Agricultural & Marine Sciences, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, OmanDepartment of Biochemistry, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, OmanDepartment of Microbiology and Immunology, Sultan Qaboos University Hospital, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, OmanDepartment of Microbiology and Immunology, Sultan Qaboos University Hospital, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, OmanDepartment of Microbiology and Immunology, Sultan Qaboos University Hospital, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, OmanDepartment of Chemistry, College of Science, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, OmanDepartment of Allied Health Sciences, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, OmanDepartments 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, CanadaDepartment of Medicine, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 50, Muscat P.C. 123, OmanHigh-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 (<i>p</i> < 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.https://www.mdpi.com/1420-3049/26/12/3624epithelial ovarian cancercisplatin resistanceMalforminA1apoptosis |
| spellingShingle | 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 Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis Molecules epithelial ovarian cancer cisplatin resistance MalforminA1 apoptosis |
| title | Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis |
| title_full | Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis |
| title_fullStr | Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis |
| title_full_unstemmed | Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis |
| title_short | Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis |
| title_sort | malformin a1 ma1 sensitizes chemoresistant ovarian cancer cells to cisplatin induced apoptosis |
| topic | epithelial ovarian cancer cisplatin resistance MalforminA1 apoptosis |
| url | https://www.mdpi.com/1420-3049/26/12/3624 |
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