Verrucarin A, a protein synthesis inhibitor, induces growth inhibition and apoptosis in breast cancer cell lines MDA-MB-231 and T47D.

Abstract

Verrucarin A (VA), a protein synthesis inhibitor, derived from the pathogen fungus Myrothecium verrucaria, inhibits growth of leukemia cell lines and activates caspases and apoptosis and inflammatory signaling in macrophages. We have investigated VA-induced growth inhibition in breast cancer cells MDA-MB-231 and T47D and, particularly, the mechanism of VA-induced apoptosis. VA treatment brought about apoptotic cell death in a dose- and time-dependent manner which was associated with chromatin condensation, cell shrinkage, nuclear fragmentation and intracellular ROS production. Mitochondrial membrane depolarization, activation of caspase-3, down-regulation of Bcl-2 expression and up-regulation of Bax and p53 expression were observed. VA thus affects the viability of both the breast cancer cells by triggering ROS-mediated intrinsic mechanism of apoptosis.

• Authors: Kandasamy Palanivel, Veerasamy Kanimozhi, Balamuthu Kadalmani, Mohammad Abdulkader Akbarsha
• Journal: Biotechnology letters (Biotechnol Lett) Vol. 35 Issue 9 Pg. 1395-403 (Sep 2013) ISSN: 1573-6776 [Electronic] Netherlands
• PMID: 23690045 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Immunologic Factors
• Protein Synthesis Inhibitors
• Trichothecenes
• muconomycin A

Topics

• Antineoplastic Agents (isolation & purification, pharmacology)
• Apoptosis
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Female
• Humans
• Hypocreales (chemistry)
• Immunologic Factors (isolation & purification, pharmacology)
• Macrophages (drug effects)
• Protein Synthesis Inhibitors (isolation & purification, pharmacology)
• Trichothecenes (isolation & purification, pharmacology)