Cytotoxic phytochemicals from the crude extract of Tetrapleura tetraptera fruits towards multi-factorial drug resistant cancer cells.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Tetrapleura tetraptera is an African medicinal spice used in traditional medicine to treat several ailments including cancer.

AIM OF THE STUDY:

The present study was designed to evaluate the cytotoxicity of the dichloromethane-methanol (1:1) extract of the fruits of Tetrapleura tetraptera (TTF) and its constituents: (3R, 4S)-3,4-dimethyloxetan-2-one (1), luteolin (2), stigmasterol (4), 3-O-[6'-O-undecanoyl-β-D-glucopyranosyl]stigmasterol (6), olean-12-en-3-β-O-D-glucopyranoside (7), 3-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosylurs-12-en-28-oic acid (8), 3-O-β-D-glucopyranosyl-(1 → 3)-β-D-glucopyranosyl-27-hydroxyolean-12-ene-28-oic acid (9), methyl-O-β-D-glucopyranoside (10), β-D-fructofuranosyl-(2 → 1)-β-D-glucopyranoside (11) towards a panel of cancer cell lines including MDR phenotypes. The cellular mode of induction of apoptosis by TTF and compound 7 was further investigated.

MATERIALS AND METHODS:

The resazurin reduction assay (RRA) was applied to determine the cytotoxicity of the studied samples. The cell cycle (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP; JC-1) and reactive oxygen species (ROS; H2DCFH-DA) were measured by flow cytometry. Column chromatography was used for the purification of TTF, whilst nuclear magnetic resonance (NMR) spectroscopic analysis was applied for structural elucidation.

RESULTS:

The botanical, TTF and the phytochemicals, 2, 7, 8 and 9 as well as doxorubicin exerted cytotoxicity against 9 cancer cell lines including drug-sensitive and drug resistant phenotypes. TTF, compound 7 and doxorubicin were the most active samples, and displayed IC50 values ranging from 10.27 μg/mL (in CCRF-CEM leukemia cells) to 23.61 μg/mL (against HCT116 p53-/- colon adenocarcinoma cells) for TTF, from 4.76 μM (against CCRF-CEM cells) to 12.92 μM (against HepG2 hepatocarcinoma cells) for compound 7, and from 0.02 μM (against CCRF-CEM cells) to 122.96 μM (against CEM/ADR5000 cells) for doxorubicin. TTF induced apoptosis in CCRF-CEM cells through MMP alteration and increased ROS production while compound 7 induced apoptosis mediated by caspases activation, MMP alteration and increased ROS production.

CONCLUSION:

Tetrapleura tetraptera and some of its constituents, mostly compound 7 are good cytotoxic natural products that should be explored in depth to develop new drugs to fight cancers.

• Authors: Armelle T Mbaveng, Godloves F Chi, Idrios N Bonsou, Japheth O Ombito, Samuel O Yeboah, Victor Kuete, Thomas Efferth
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 267 Pg. 113632 (Mar 01 2021) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 33253828 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Caspases
• Phytochemicals
• Plant Extracts
• Reactive Oxygen Species

Topics

• Humans
• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Caspases (metabolism)
• Dose-Response Relationship, Drug
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Fruit (chemistry)
• HCT116 Cells
• Hep G2 Cells
• Inhibitory Concentration 50
• Membrane Potential, Mitochondrial (drug effects)
• Neoplasms (drug therapy, metabolism, pathology)
• Oxidative Stress (drug effects)
• Phytochemicals (isolation & purification, pharmacology)
• Plant Extracts (isolation & purification, pharmacology)
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• Tetrapleura (chemistry)