title: Anticancer activity of Ophiobolin A, isolated from the endophytic fungus Bipolaris setariae.
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.
authors.affiliation: a Department of Pharmacology , Piramal Enterprises Limited , Mumbai , Maharashtra , India.
authors.forename: Dimple R
authors.initials: DR
authors.lastname: Bhatia
authors.affiliation: a Department of Pharmacology , Piramal Enterprises Limited , Mumbai , Maharashtra , India.
authors.forename: Payal
authors.initials: P
authors.lastname: Dhar
authors.affiliation: b Department of Natural Products , Piramal Enterprises Limited , Mumbai , Maharashtra , India.
authors.forename: Varun
authors.initials: V
authors.lastname: Mutalik
authors.affiliation: b Department of Natural Products , Piramal Enterprises Limited , Mumbai , Maharashtra , India.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Deshmukh
authors.affiliation: b Department of Natural Products , Piramal Enterprises Limited , Mumbai , Maharashtra , India.
authors.forename: Shilpa A
authors.initials: SA
authors.lastname: Verekar
authors.affiliation: c Department of Chemistry , Piramal Enterprises Limited , Mumbai , Maharashtra , India.
authors.forename: Dattatraya C
authors.initials: DC
authors.lastname: Desai
authors.affiliation: c Department of Chemistry , Piramal Enterprises Limited , Mumbai , Maharashtra , India.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Kshirsagar
authors.affiliation: d School of Biosciences and Technology , VIT University , Vellore , Tamil Nadu , India.
authors.forename: Padma
authors.initials: P
authors.lastname: Thiagarajan
authors.affiliation: a Department of Pharmacology , Piramal Enterprises Limited , Mumbai , Maharashtra , India.
authors.forename: Veena
authors.initials: V
authors.lastname: Agarwal
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001203:Ascomycota / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D060026:Endophytes / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D054830:Sesterterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019869:Phosphatidylinositol 3-Kinases; D054830:Sesterterpenes; D058570:TOR Serine-Threonine Kinases; C040764:ophiobolin A; C546842:MTOR protein, human
keywords: Bipolaris setariae; CDK/RB; Ophiobolin A; PI3K/mTOR; Ras/ERK