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Cytotoxic constituents from the mangrove endophytic Pestalotiopsis sp. induce G₀/G₁ cell cycle arrest and apoptosis in human cancer cells

Author:
Zhou, Jing, Li, Gang, Deng, Qin, Zheng, Dongyao, Yang, Xiaobo, Xu, Jing
Source:
Natural product research 2018 v.32 no.24 pp. 2968-2972
ISSN:
1478-6427
Subject:
Pestalotiopsis, Rhizophora mucronata, antineoplastic agents, apoptosis, cell cycle checkpoints, cytotoxicity, dose response, endophytes, flow cytometry, human cell lines, humans, inhibitory concentration 50, interphase, metabolites, mitochondria, neoplasm cells, nuclear magnetic resonance spectroscopy
Abstract:
Chemical examination of Chinese mangrove Rhizophora mucronata endophytic Pestalotiopsis sp., yielded 11 known metabolites with various structure types, including demethylincisterol A₃ (1), dankasterone B (2), (22E, 24R)-ergosta-7,9(11), 22-triene-3β, 5α, 6α-triol (3), ergosta-5,7,22-trien-3-ol (4), 5, 8-epidioxy-5, 8-ergosta-6, 22E-dien-3-ol (5), stigmastan-3-one (6), stigmast-4-en-3-one (7), stigmast-4-en-6 -ol-3-one (8), flufuran (9), (2-cis, 4-trans)-abscisic acid (10), similanpyrone B (11). Their structures were unambiguously elucidated on the basis of extensive NMR spectroscopic and mass spectrometric analyses. Compounds 1, 4, 6–9 showed significant in vitro cytotoxicity against the human cancer cell lines Hela, A549 and HepG, of which compound 1 was the most potential with IC₅₀ values reaching nM degree ranging from 0.17 to 14.16 nM. Flow cytometric investigation demonstrated that compound 1 mainly inhibited cell cycle at G₀/G₁ phase in a dose-dependent manner with a significant induction of apoptosis on the three tested cell lines. The involvement of the mitochondria in compound 1 induced apoptosis was investigated using MMP. We suggested that R. mucronata endophytic Pestalotiopsis sp. contained a potential anticancer compound demethylincisterol A₃.
Agid:
6326223