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Article Publish Status: FREE
Abstract Title:

Carnosol induces ROS-mediated beclin1-independent autophagy and apoptosis in triple negative breast cancer.

Abstract Source:

PLoS One. 2014 ;9(10):e109630. Epub 2014 Oct 9. PMID: 25299698

Abstract Author(s):

Yusra Al Dhaheri, Samir Attoub, Gaber Ramadan, Kholoud Arafat, Khuloud Bajbouj, Noushad Karuvantevida, Synan AbuQamar, Ali Eid, Rabah Iratni

Article Affiliation:

Yusra Al Dhaheri

Abstract:

BACKGROUND: In this study we investigated the in vitro and in vivo anticancer effect of carnosol, a naturally occurring polyphenol, in triple negative breast cancer.

RESULTS: We found that carnosol significantly inhibited the viability and colony growth induced G2 arrest in the triple negative MDA-MB-231. Blockade of the cell cycle was associated with increased p21/WAF1 expression and downregulation of p27. Interestingly, carnosol was found to induce beclin1-independent autophagy and apoptosis in MDA-MB-231 cells. The coexistence of both events, autophagy and apoptosis, was confirmed by electron micrography. Induction of autophagy was found to be an early event, detected within 3 h post-treatment, which subsequently led to apoptosis. Carnosol treatment also caused a dose-dependent increase in the levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2). Moreover, we show that carnosol induced DNA damage, reduced the mitochondrial potential and triggered the activation of the intrinsic and extrinsic apoptotic pathway. Furthermore, we found that carnosol induced a dose-dependent generation of reactive oxygen species (ROS) and inhibition of ROS by tiron, a ROS scavenger, blocked the induction of autophagy and apoptosis and attenuated DNA damage. To our knowledge, this is the first report to identify the induction of autophagy by carnosol.

CONCLUSION: In conclusion our findings provide strong evidence that carnosol may be an alternative therapeutic candidate against the aggressive form of breast cancer and hence deserves more exploration.

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