Tan, Chun Hoe and Sim, Dawn Su Yin and Lim, Siew Huah and Mohidin, Taznim Begam Mohd and Mohan, Gokula and Low, Yun Yee and Kam, Toh Seok and Sim, Kae Shin (2022) Antiproliferative and microtubule-stabilizing activities of two iboga-vobasine Bisindoles Alkaloids from tabernaemontana corymbosa in colorectal adenocarcinoma HT-29 cells. Planta Medica, 88 (14). pp. 1325-1340. ISSN 0032-0943, DOI https://doi.org/10.1055/a-1755-5605.
Full text not available from this repository.Abstract
Two iboga-vobasine bisindoles, 16 & PRIME;-decarbomethoxyvoacamine ( 1 ) and its 19,20-dihydro derivative, 16 & PRIME;-decarbomethoxydihydrovoacamine ( 2 ) from Tabernaemontana corymbosa exhibited potent cytotoxicity against the human colorectal adenocarcinoma HT-29 cells in our previous studies. Bisindoles 1 and 2 selectively inhibited the growth of HT-29 cells without significant cytotoxicity to normal human colon fibroblasts CCD-18Co. Treatment with bisindoles 1 and 2 suppressed the formation of HT-29 colonies via G0/G1 cell cycle arrest and induction of mitochondrial apoptosis. Owing to its higher antiproliferative activity, bisindole 2 was chosen for the subsequent studies. Bisindole 2 inhibited the formation of HT-29 spheroids (tumor-like cell aggregates) in 3D experiments in a dose-dependent manner, while an in vitro tubulin polymerization assay and molecular docking analysis showed that bisindole 2 is a microtubule-stabilizing agent which is predicted to bind at the beta -tubulin subunit at the taxol-binding site. The binding resulted in the generation of ROS, which consequently activated the oxidative stress-related cell cycle arrest and apoptotic pathways, viz., JNK/p38, p21(Cip1)/Chk1, and p21 (Cip1)/Rb/E2F, as shown by microarray profiling.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Education, Malaysia [Grant No: FRGS/1/2019/STG01/UM/02/23 (FP100-2019A)] |
| Uncontrolled Keywords: | Tabernaemontana corymbosa; Apocynaceae; 16'-Decarbomethoxyvoacamine; 16'-Decarbomethoxydihydrovoacamine; Apoptosis; G0/G1 phase arrest |
| Subjects: | Q Science > QD Chemistry R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Faculty of Science > Institute of Biological Sciences Faculty of Science > Department of Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 04 Nov 2025 06:49 |
| Last Modified: | 04 Nov 2025 06:49 |
| URI: | http://eprints.um.edu.my/id/eprint/40758 |
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