Cytotoxicity of anthraquinones from the roots of Pentas schimperi towards multi-factorial drug-resistant cancer cells.

Abstract

INTRODUCTION:

Multidrug resistance in cancer represents a major problem in chemotherapy. The present study was designed to assess the cytotoxicity of anthraquinones from Pentas schimperi, namely damnacanthal (1), damnacanthol (2), 3-hydroxy-2-hydroxymethyl anthraquinone (3) and schimperiquinone B (4) against nine drug-sensitive and multidrug resistant (MDR) cancer cell lines.

METHODS:

The resazurin reduction assay was used to evaluate the cytotoxicity of the above compounds, whilst caspase-Glo assay was used to detect the activation of caspases enzymes by compounds 1 and 2. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species were all analyzed via flow cytometry.

RESULTS:

Anthraquinones 1 and 2 displayed cytotoxic effects with IC50 values below 81 μM on all the nine tested cancer cell lines whilst 3 and 4 displayed selective activities. The recorded IC50 values for compounds 1 and 2 ranged from 3.12 μM and 12.18 μM (towards leukemia CCRF-CEM cells) and from 30.32 μM and 80.11 μM (towards gliobastoma U87MG.ΔEGFR cells) respectively, and from 0.20 μM (against CCRF-CEM cells) to 195.12 μM (against CEM/ADR5000 cells) for doxorubicin. Compounds 1 and 2 induced apoptosis in CCRF-CEM leukemia cells, mediated by the disruption of the MMP and increase in ROS production.

CONCLUSIONS:

Anthraquinones from Pentas schimperi and mostly 1 and 2 are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug resistant cancers.

• Authors: Victor Kuete, Arno R Nanfack Donfack, Armelle T Mbaveng, Maen Zeino, Pierre Tane, Thomas Efferth
• Journal: Investigational new drugs (Invest New Drugs) Vol. 33 Issue 4 Pg. 861-9 (Aug 2015) ISSN: 1573-0646 [Electronic] United States
• PMID: 26115800 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Anthraquinones (isolation & purification, pharmacology)
• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Caspases (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Plant Extracts
• Plant Roots
• Reactive Oxygen Species (metabolism)
• Rubiaceae