Anticancer activity of Ophiobolin A, isolated from the endophytic fungus Bipolaris setariae. Issue 12 (17th June 2016)

• Record Type: Journal Article
• Authors: Bhatia, Dimple R.; Dhar, Payal; Mutalik, Varun; Deshmukh, Sunil Kumar; Verekar, Shilpa A.; Desai, Dattatraya C.; Kshirsagar, Rajendra; Thiagarajan, Padma; Agarwal, Veena
• Is Part Of: Natural product research. Volume 30:Issue 12(2016)
• Page Start: 1455
• Page End: 1458
• Publication Date: 2016-06-17
• Subjects: Ophiobolin A -- Bipolaris setariae -- PI3K/mTOR -- Ras/ERK -- CDK/RB; Natural products -- Periodicals; Natural products -- Research -- Periodicals; Biological Factors -- Periodicals; Biological Products -- Periodicals; 547
• DOI: 10.1080/14786419.2015.1062760
• Languages: English
• ISSNs: 1478-6419

Abstract

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, 1 H NMR, 13 C 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. Graphical abstract: