The genus Claviceps (Clavicipitaceae) is noted for producing ergot alkaloids that cause ergotism. Claviceps yanagawaensis, a parasite of Zoysia japonica (family: Poaceae), has been isolated in Japan. Bioactivity scree...The genus Claviceps (Clavicipitaceae) is noted for producing ergot alkaloids that cause ergotism. Claviceps yanagawaensis, a parasite of Zoysia japonica (family: Poaceae), has been isolated in Japan. Bioactivity screening showed that a methanol extract from a rice culture of C. yanagawaensis was cytotoxic to cancer cells. In our search for active substances, the new secalonic acid analogues (-)-5-epi-F-7 (1) and ergochrysin C (2) and a new benzoic acid analogue, dimethyl bigutol (3), were isolated along with the known compounds 3,4-dihydroxy-5-(3-methyl-2-buten-1-yl)benzoic acid (4) and methyl veratrate (5). The structures of 1 - 3 were elucidated by NMR, MS, and circular dichroism spectroscopy. MTT assays of 1 - 5 using cancer cell lines (HepG2, HL60, HT29, PANC-1, and T98G) showed that 1 - 4 exhibited cytotoxicity against cancer cells.展开更多
Secalonic acid D(SAD) could inhibit cell growth in not only sensitive cells but also multidrug resistant(MDR) cells. However, the molecular mechanisms need to be elucidated. Here, we identified that SAD possessed pote...Secalonic acid D(SAD) could inhibit cell growth in not only sensitive cells but also multidrug resistant(MDR) cells. However, the molecular mechanisms need to be elucidated. Here, we identified that SAD possessed potent cytotoxicity in 3 pairs of MDR and their parental sensitive cells including S1-MI-80 and S1,H460/MX20 and H460, MCF-7/ADR and MCF-7 cells. Furthermore, SAD induced cell G2/M phase arrest via the downregulation of cyclin B1 and the increase of CDC2 phosphorylation. Importantly, JNK pathway upregulated the expression of c-Jun in protein level and increased c-Jun phosphorylation induced by SAD, which was linked to cell apoptosis via c-Jun/Src/STAT3 pathway. To investigate the mechanisms of upregulation of c-Jun protein by SAD, the mR NA expression level and degradation of c-Jun were examined. We found that SAD did not alter the mR NA level of c-Jun but inhibited its proteasome-dependent degradation. Taken together, these results implicate that SAD induces cancer cell death through c-Jun/Src/STAT3 signaling axis by inhibiting the proteasome-dependent degradation of c-Jun in both sensitive cells and ATP-binding cassette transporter sub-family G member 2(ABCG2)-mediated MDR cells.展开更多
In vitro bioassay screening systemically,we find that the crude extract of mangrove endophytic fungus Paecilomyces sp.(tree1-7)from the Taiwan Strait showed strong inhibiting to KB cells,and isolate three isomeric com...In vitro bioassay screening systemically,we find that the crude extract of mangrove endophytic fungus Paecilomyces sp.(tree1-7)from the Taiwan Strait showed strong inhibiting to KB cells,and isolate three isomeric compounds,secalonic acid A(1),penicillixanthone A(2),paecilin A(3).Their structures are elucidated by spectral data,and the 3 is the first time to be isolated from marine fungus.The results of primary bioactivity experiments indicate that the three compounds display strong inhibiting activity to KB cell in vitro,and 1 show inhibiting to KB and KBv cells at IC50 less 1.57nmol/mL,2 at IC50 less 1.22nmol/mL and 3 at IC50 40,50nmol/mL,respectively.展开更多
文摘The genus Claviceps (Clavicipitaceae) is noted for producing ergot alkaloids that cause ergotism. Claviceps yanagawaensis, a parasite of Zoysia japonica (family: Poaceae), has been isolated in Japan. Bioactivity screening showed that a methanol extract from a rice culture of C. yanagawaensis was cytotoxic to cancer cells. In our search for active substances, the new secalonic acid analogues (-)-5-epi-F-7 (1) and ergochrysin C (2) and a new benzoic acid analogue, dimethyl bigutol (3), were isolated along with the known compounds 3,4-dihydroxy-5-(3-methyl-2-buten-1-yl)benzoic acid (4) and methyl veratrate (5). The structures of 1 - 3 were elucidated by NMR, MS, and circular dichroism spectroscopy. MTT assays of 1 - 5 using cancer cell lines (HepG2, HL60, HT29, PANC-1, and T98G) showed that 1 - 4 exhibited cytotoxicity against cancer cells.
基金supported by grants from the National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program” (No. 2018ZX09711002, China)Science and Technology Foundation of Guangdong Province (No. 2016A030312014, China)+1 种基金Guangzhou Science and Technology Program (No. 201707010048, China)from the Scientific and Technological Leading Talent Project of Guangdong Province (2015, China)
文摘Secalonic acid D(SAD) could inhibit cell growth in not only sensitive cells but also multidrug resistant(MDR) cells. However, the molecular mechanisms need to be elucidated. Here, we identified that SAD possessed potent cytotoxicity in 3 pairs of MDR and their parental sensitive cells including S1-MI-80 and S1,H460/MX20 and H460, MCF-7/ADR and MCF-7 cells. Furthermore, SAD induced cell G2/M phase arrest via the downregulation of cyclin B1 and the increase of CDC2 phosphorylation. Importantly, JNK pathway upregulated the expression of c-Jun in protein level and increased c-Jun phosphorylation induced by SAD, which was linked to cell apoptosis via c-Jun/Src/STAT3 pathway. To investigate the mechanisms of upregulation of c-Jun protein by SAD, the mR NA expression level and degradation of c-Jun were examined. We found that SAD did not alter the mR NA level of c-Jun but inhibited its proteasome-dependent degradation. Taken together, these results implicate that SAD induces cancer cell death through c-Jun/Src/STAT3 signaling axis by inhibiting the proteasome-dependent degradation of c-Jun in both sensitive cells and ATP-binding cassette transporter sub-family G member 2(ABCG2)-mediated MDR cells.
文摘In vitro bioassay screening systemically,we find that the crude extract of mangrove endophytic fungus Paecilomyces sp.(tree1-7)from the Taiwan Strait showed strong inhibiting to KB cells,and isolate three isomeric compounds,secalonic acid A(1),penicillixanthone A(2),paecilin A(3).Their structures are elucidated by spectral data,and the 3 is the first time to be isolated from marine fungus.The results of primary bioactivity experiments indicate that the three compounds display strong inhibiting activity to KB cell in vitro,and 1 show inhibiting to KB and KBv cells at IC50 less 1.57nmol/mL,2 at IC50 less 1.22nmol/mL and 3 at IC50 40,50nmol/mL,respectively.
