Monoterpene bisindole alkaloids, from the African medicinal plant Tabernaemontana elegans, induce apoptosis in HCT116 human colon carcinoma cells.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Tabernaemontana elegans is a medicinal plant used in African traditional medicine to treat several ailments including cancer. The aims of the present study were to identify anti-cancer compounds, namely apoptosis inducers, from Tabernaemontana elegans, and hence to validate its usage in traditional medicine.

METHODS AND MATERIALS:

Six alkaloids, including four monomeric indole (1-3, and 6) and two bisindole (4 and 5) alkaloids, were isolated from the methanolic extract of Tabernaemontana elegans roots. The structures of these compounds were characterized by 1D and 2D NMR spectroscopic and mass spectrometric data. Compounds 1-6 along with compound 7, previously isolated from the leaves of the same species, were evaluated for in vitro cytotoxicity against HCT116 human colon carcinoma cells by the MTS metabolism assay. The cytotoxicity of the most promising compounds was corroborated by Guava-ViaCount flow cytometry assays. Selected compounds were next studied for apoptosis induction activity in HCT116 cells, by evaluation of nuclear morphology following Hoechst staining, and by caspase-3 like activity assays.

RESULTS:

Among the tested compounds (1-7), the bisindole alkaloids tabernaelegantine C (4) and tabernaelegantinine B (5) were found to be cytotoxic to HCT116 cells at 20 µM, with compound 5 being more cytotoxic than the positive control 5-Fluorouracil (5-FU), at a similar dose. In fact, even at 0.5 µM, compound 5 was more potent than 5-FU. Compounds 4 and 5 induced characteristic patterns of apoptosis in HCT116 cancer cells including, cell shrinkage, condensation, fragmentation of the nucleus, blebbing of the plasma membrane and chromatin condensation. Further, general caspase-3-like activity was increased in cells exposed to compounds 4 and 5, corroborating the nuclear morphology evaluation assays.

CONCLUSIONS:

Bisindole alkaloids tabernaelegantine C (4) and tabernaelegantinine B (5) were characterized as potent apoptosis inducers in HCT116 human colon carcinoma cells and as possible lead/scaffolds for the development of anti-cancer drugs. This study substantiates the usage of Tabernaemontana elegans in traditional medicine to treat cancer.

• Authors: Tayyab A Mansoor, Pedro M Borralho, Saikat Dewanjee, Silva Mulhovo, Cecília M P Rodrigues, Maria-José U Ferreira
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 149 Issue 2 Pg. 463-70 (Sep 16 2013) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 23872252 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Alkaloids
• Antineoplastic Agents
• Monoterpenes
• Plant Extracts
• Caspase 3

Topics

• Alkaloids (pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Colonic Neoplasms
• HCT116 Cells
• Humans
• Monoterpenes (pharmacology)
• Plant Extracts
• Plant Roots
• Plants, Medicinal
• Tabernaemontana