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
Document Type
Article
Publication Date
5-28-2021
Abstract
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.
Keywords
Macroline-akuammiline bisindole, Microtubule-stabilizing agents, Spectroscopic data, Tubulin Polymerization
Divisions
Science
Funders
Universiti Malaya,MOHE, Malaysia (FRGS/1/2019/STG01/UM/02/23)
Publication Title
Journal of Natural Products
Volume
84
Issue
5
Publisher
American Chemical Society
Publisher Location
1155 16TH ST, NW, WASHINGTON, DC 20036 USA