The Bisindole Alkaloids Angustilongines M and A from 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 (), was isolated from the methanolic extract of . 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 (). Compounds and 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 β-tubulin subunit at the Taxol-binding site.