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18β-glycyrrhetinic acid induces apoptosis through modulation of Akt/FOXO3a/Bim pathway in human breast cancer MCF-7 cells
Journal of cellular physiology, 2012-05, Vol.227 (5), p.1923-1931
Sharma, Gunjan
Kar, Susanta
Palit, Shreyasi
Das, Pijush K.
2012
Details
Autor(en) / Beteiligte
Sharma, Gunjan
Kar, Susanta
Palit, Shreyasi
Das, Pijush K.
Titel
18β-glycyrrhetinic acid induces apoptosis through modulation of Akt/FOXO3a/Bim pathway in human breast cancer MCF-7 cells
Ist Teil von
Journal of cellular physiology, 2012-05, Vol.227 (5), p.1923-1931
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2012
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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.
Sprache
Englisch
Identifikatoren
ISSN: 0021-9541
eISSN: 1097-4652
DOI: 10.1002/jcp.22920
Titel-ID: cdi_proquest_miscellaneous_917854342
Format
–
Schlagworte
Animals
,
Apoptosis - drug effects
,
Apoptosis Regulatory Proteins - genetics
,
Apoptosis Regulatory Proteins - metabolism
,
Bcl-2-Like Protein 11
,
Caspase 9 - genetics
,
Caspase 9 - metabolism
,
Cell Line, Tumor
,
Enzyme Activation
,
Female
,
Forkhead Box Protein O3
,
Forkhead Transcription Factors - genetics
,
Forkhead Transcription Factors - metabolism
,
Glycyrrhetinic Acid - analogs & derivatives
,
Glycyrrhetinic Acid - pharmacology
,
Humans
,
Membrane Proteins - genetics
,
Membrane Proteins - metabolism
,
Mitochondria - drug effects
,
Mitochondria - metabolism
,
Proto-Oncogene Proteins - genetics
,
Proto-Oncogene Proteins - metabolism
,
Proto-Oncogene Proteins c-akt - metabolism
,
Proto-Oncogene Proteins c-bcl-2 - metabolism
,
RNA, Small Interfering - genetics
,
RNA, Small Interfering - metabolism
,
Signal Transduction - drug effects
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