Cytotoxic constituents from the mangrove endophytic <i>Pestalotiopsis</i> sp<i>.</i> induce G<sub>0</sub>/G<sub>1</sub> cell cycle arrest and apoptosis in human cancer cells

<p>Chemical examination of Chinese mangrove <i>Rhizophora mucronata</i> endophytic <i>Pestalotiopsis</i> sp<i>.</i>, yielded  11 known metabolites with various structure types, including demethylincisterol A<sub>3</sub> (<b>1</b>), dankasterone B (<b>2</b>), (22<i>E</i>, 24<i>R</i>)-ergosta-7,9(11), 22-triene-3<i>β</i>, 5<i>α</i>, 6<i>α</i>-triol (<b>3</b>), ergosta-5,7,22-trien-3-ol (<b>4</b>), 5, 8-epidioxy-5, 8-ergosta-6, 22<i>E</i>-dien-3-ol (<b>5</b>), stigmastan-3-one (<b>6</b>), stigmast-4-en-3-one (<b>7</b>), stigmast-4-en-6 -ol-3-one (<b>8</b>), flufuran (<b>9</b>), (2-<i>cis</i>, 4-<i>trans</i>)-abscisic acid (<b>10</b>), similanpyrone B (<b>11</b>). Their structures were unambiguously elucidated on the basis of extensive NMR spectroscopic and mass spectrometric analyses. Compounds <b>1</b>, <b>4</b>, <b>6–9</b> showed significant <i>in vitro</i> cytotoxicity against the human cancer cell lines Hela, A549 and HepG, of which compound <b>1</b> was the most potential with IC<sub>50</sub> values reaching nM degree ranging from 0.17 to 14.16 nM. Flow cytometric investigation demonstrated that compound <b>1</b> mainly inhibited cell cycle at G<sub>0</sub>/G<sub>1</sub> 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 <b>1</b> induced apoptosis was investigated using MMP. We suggested that <i>R. mucronata</i> endophytic <i>Pestalotiopsis</i> sp<i>.</i> contained a potential anticancer compound demethylincisterol A<sub>3</sub>.</p>