Anticancer activity of Ophiobolin A,isolated from the endophytic fungus Bipolaris setariae |
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| Authors: | Dimple R. Bhatia Payal Dhar Varun Mutalik Sunil Kumar Deshmukh Shilpa A. Verekar Dattatraya C. Desai |
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| Affiliation: | 1. Department of Pharmacology, Piramal Enterprises Limited, Mumbai, Maharashtra, Indiadimplebhatia2009@gmail.com;3. Department of Pharmacology, Piramal Enterprises Limited, Mumbai, Maharashtra, India;4. Department of Natural Products, Piramal Enterprises Limited, Mumbai, Maharashtra, India;5. Department of Chemistry, Piramal Enterprises Limited, Mumbai, Maharashtra, India |
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| Abstract: | The present work describes the anticancer activity of Ophiobolin A isolated from the endophytic fungus Bipolaris setariae. Ophiobolin A was isolated using preparative HPLC and its structure was confirmed by HRMS, 1H NMR, 13C NMR, COSY, DEPT, HSQC and HMBC. It inhibited solid and haematological cancer cell proliferation with IC50 of 0.4–4.3 μM. In comparison, IC50 against normal cells was 20.9 μM. It was found to inhibit the phosphorylation of S6 (IC50 = 1.9 ± 0.2 μM), ERK (IC50 = 0.28 ± 0.02 μM) and RB (IC50 = 1.42 ± 0.1 μM), the effector proteins of PI3K/mTOR, Ras/Raf/ERK and CDK/RB pathways, respectively. It induced apoptosis and inhibited cell cycle progression in MDA-MB-231 cancer cells with concomitant inhibition of signalling proteins. Thus, this study reveals that anticancer activity of Ophiobolin A is associated with simultaneous inhibition of multiple oncogenic signalling pathways namely PI3K/mTOR, Ras/Raf/ERK and CDK/RB. |
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| Keywords: | Ophiobolin A Bipolaris setariae PI3K/mTOR Ras/ERK CDK/RB |
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