This article was published online on 23 January 2012. An error was subsequently identified: “(Concur)” was inadvertently introduced into the article title by production error. This notice is included in the online and print versions to indicate that both have been corrected 25 January 2012.
Original Research Article
18β-glycyrrhetinic acid induces apoptosis through modulation of Akt/FOXO3a/Bim pathway in human breast cancer MCF-7 cells†
Version of Record online: 23 JAN 2012
Copyright © 2011 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 227, Issue 5, pages 1923–1931, May 2012
How to Cite
Sharma, G., Kar, S., Palit, S. and Das, P. K. (2012), 18β-glycyrrhetinic acid induces apoptosis through modulation of Akt/FOXO3a/Bim pathway in human breast cancer MCF-7 cells. J. Cell. Physiol., 227: 1923–1931. doi: 10.1002/jcp.22920
- Issue online: 23 JAN 2012
- Version of Record online: 23 JAN 2012
- Accepted manuscript online: 5 JUL 2011 10:28AM EST
- Manuscript Accepted: 21 JUN 2011
- Manuscript Received: 21 JAN 2011
- Supra Institutional Project. Grant Number: SIP 007
- Network Project. Grant Number: NWP 0038
- Council of Scientific and Industrial Research, Government of India
Triterpenes found in plants display a multitude of biological activities, including anti-tumor properties. The present study investigates the effect of 18β-glycyrrhetinic acid (GRA) a pentacyclic triterpenoid of the β-amyrin type, isolated from the root of Licorice (Glycyrrhizza glabra) on human breast cancer cells, MCF-7. GRA showed potent inhibitory effects on MCF-7 proliferation in a concentration- and time-dependent manner without affecting immortalized normal mammary epithelial cell line (MCF-10A). Growth inhibition of MCF-7 cells by GRA occurred through apoptosis, as evident from phosphatidyl serine externalization and DNA fragmentation. Apoptosis was primarily mediated through mitochondrial death cascade as evidenced by loss of mitochondrial membrane potential, release of cytochrome c and activation of caspase-9. GRA induced an increase in Bax:Bcl-2 ratio along with a significant increase in the protein level of the BH3 protein Bim. SiRNA-mediated knock down of Bim markedly attenuated GRA-mediated apoptosis. Profiling of transcriptional regulators of Bim revealed a role of Forkhead box O 3a transcription factor (FOXO3a) as judged by increased expression and nuclear translocation of FOXO3a. Silencing of FOXO3a resulted in marked attenuation in the expression of Bim as well as protection against GRA-mediated apoptosis. Furthermore, GRA-induced activation and nuclear localization of FOXO3a was associated with a reduced activity of Akt kinase. These results suggest that GRA induces apoptosis in human breast carcinoma MCF-7 cells via caspase activation and modulation of Akt/FOXO3a pathway. J. Cell. Physiol. 227: 1923–1931, 2012. © 2011 Wiley Periodicals, Inc.