The Bisindole Alkaloids Angustilongines M and A from Alstonia penangiana Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization
A new linearly fused macroline-sarpagine bisindole, angustilongine M (1), was isolated from the methanolic extract of Alstonia penangiana. The structure of the alkaloid was elucidated based on analysis of the spectroscopic data, and its biological activity was evaluated together with another previou...
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my.um.eprints.285152022-03-03T01:43:24Z http://eprints.um.edu.my/28515/ The Bisindole Alkaloids Angustilongines M and A from Alstonia penangiana Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization Tan, Chun-Hoe Yeap, Joanne Soon-Yee Lim, Siew-Huah Low, Yun-Yee Sim, Kae-Shin Kam, Toh-Seok QK Botany RM Therapeutics. Pharmacology A new linearly fused macroline-sarpagine bisindole, angustilongine M (1), was isolated from the methanolic extract of Alstonia penangiana. The structure of the alkaloid was elucidated based on analysis of the spectroscopic data, and its biological activity was evaluated together with another previously reported macroline-akuammiline bisindole from the same plant, angustilongine A (2). Compounds 1 and 2 showed pronounced in vitro growth inhibitory activity against a wide panel of human cancer cell lines. In particular, the two compounds showed potent and selective antiproliferative activity against HT-29 cells, as well as strong growth inhibitory effects against HT-29 spheroids. Cell death mechanistic studies revealed that the compounds induced mitochondrial apoptosis and G0/G1 cell cycle arrest in HT-29 cells in a time-dependent manner, while in vitro tubulin polymerization assays and molecular docking analysis showed that the compounds are microtubule-stabilizing agents, which are predicted to bind at the beta-tubulin subunit at the Taxol-binding site. American Chemical Society 2021-05-28 Article PeerReviewed Tan, Chun-Hoe and Yeap, Joanne Soon-Yee and Lim, Siew-Huah and Low, Yun-Yee and Sim, Kae-Shin and Kam, Toh-Seok (2021) The Bisindole Alkaloids Angustilongines M and A from Alstonia penangiana Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization. Journal of Natural Products, 84 (5). pp. 1524-1533. ISSN 0163-3864, DOI https://doi.org/10.1021/acs.jnatprod.1c00013 <https://doi.org/10.1021/acs.jnatprod.1c00013>. 10.1021/acs.jnatprod.1c00013 |
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QK Botany RM Therapeutics. Pharmacology Tan, Chun-Hoe Yeap, Joanne Soon-Yee Lim, Siew-Huah Low, Yun-Yee Sim, Kae-Shin Kam, Toh-Seok The Bisindole Alkaloids Angustilongines M and A from Alstonia penangiana Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization |
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A new linearly fused macroline-sarpagine bisindole, angustilongine M (1), was isolated from the methanolic extract of Alstonia penangiana. The structure of the alkaloid was elucidated based on analysis of the spectroscopic data, and its biological activity was evaluated together with another previously reported macroline-akuammiline bisindole from the same plant, angustilongine A (2). Compounds 1 and 2 showed pronounced in vitro growth inhibitory activity against a wide panel of human cancer cell lines. In particular, the two compounds showed potent and selective antiproliferative activity against HT-29 cells, as well as strong growth inhibitory effects against HT-29 spheroids. Cell death mechanistic studies revealed that the compounds induced mitochondrial apoptosis and G0/G1 cell cycle arrest in HT-29 cells in a time-dependent manner, while in vitro tubulin polymerization assays and molecular docking analysis showed that the compounds are microtubule-stabilizing agents, which are predicted to bind at the beta-tubulin subunit at the Taxol-binding site. |
format |
Article |
author |
Tan, Chun-Hoe Yeap, Joanne Soon-Yee Lim, Siew-Huah Low, Yun-Yee Sim, Kae-Shin Kam, Toh-Seok |
author_facet |
Tan, Chun-Hoe Yeap, Joanne Soon-Yee Lim, Siew-Huah Low, Yun-Yee Sim, Kae-Shin Kam, Toh-Seok |
author_sort |
Tan, Chun-Hoe |
title |
The Bisindole Alkaloids Angustilongines M and A from Alstonia penangiana Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization |
title_short |
The Bisindole Alkaloids Angustilongines M and A from Alstonia penangiana Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization |
title_full |
The Bisindole Alkaloids Angustilongines M and A from Alstonia penangiana Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization |
title_fullStr |
The Bisindole Alkaloids Angustilongines M and A from Alstonia penangiana Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization |
title_full_unstemmed |
The Bisindole Alkaloids Angustilongines M and A from Alstonia penangiana Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization |
title_sort |
bisindole alkaloids angustilongines m and a from alstonia penangiana induce mitochondrial apoptosis and g0/g1 cell cycle arrest in ht-29 cells through promotion of tubulin polymerization |
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American Chemical Society |
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2021 |
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http://eprints.um.edu.my/28515/ |
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