Mechanism of the malabaricone C-induced toxicity to the MCF-7 cell line.

Abstract

In this study, we studied the mechanism of the cytotoxicity of malabaricone C (mal C) against human breast cancer MCF-7 cell line. Mal C dose-dependently increased the sub G1 cell population, associated with cytoplasmic oligonucleosome formation and chromatin condensation. The mal C-induced apoptosis led to mitochondrial damage as revealed by fluorescence microscopy and flow cytometry of the JC-1-stained cells as well as from the release of mitochondrion-specific nuclease proteins AIF and endo G. Mal C also released intracellular Ca(2+) from the MCF-7 cells, but the Ca(2+)-modulators BAPTA-AM and Ru360 only partially abrogated the apoptosis. The calpain activation by mal C did not have any effect on its cytotoxicity. On the other hand, after mal C treatment significant lysosomal membrane permeabilization (LMP), along with release of cathepsin B, as well as Bid-cleavage and its translocation to mitochondria were observed much earlier than the mitochondrial damage. This suggested that cytotoxicity of mal C against human MCF-7 human breast cancer cell line may proceed through LMP as the initial event that triggered a caspase-independent, but cathepsin B and t-Bid-dependent intrinsic mitochondrial apoptotic pathway. A significant accumulation of cells in the S or G2-M phases along with upregulation of the cyclins E and A due to mal C exposure promises it to be a potential anti-cancer agent.

• Authors: M Tyagi, B S Patro, S Chattopadhyay
• Journal: Free radical research (Free Radic Res) Vol. 48 Issue 4 Pg. 466-77 (Apr 2014) ISSN: 1029-2470 [Electronic] England
• PMID: 24456233 (Publication Type: Journal Article)

Chemical References

• Resorcinols
• malabaricone C

Topics

• Apoptosis
• Breast Neoplasms (metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Female
• Humans
• MCF-7 Cells
• Resorcinols (metabolism)
• Signal Transduction