Carnosol induces ROS-mediated beclin1-independent autophagy and apoptosis in triple negative breast cancer
المؤلف | Al Dhaheri, Y. |
المؤلف | Attoub, S. |
المؤلف | Ramadan, G. |
المؤلف | Arafat, K. |
المؤلف | Bajbouj, K. |
المؤلف | Karuvantevida, N. |
المؤلف | AbuQamar, S. |
المؤلف | Eid, A. |
المؤلف | Iratni, R. |
تاريخ الإتاحة | 2016-02-08T14:21:26Z |
تاريخ النشر | 2014-10 |
اسم المنشور | PLoS ONE |
المصدر | Scopus |
الاقتباس | Al Dhaheri, Y., Attoub, S., Ramadan, G., Arafat, K., Bajbouj, K., Karuvantevida, N., AbuQamar, S., Eid, A., Iratni, R. "Carnosol induces ROS-mediated beclin1-independent autophagy and apoptosis in triple negative breast cancer." (2014) PLoS ONE, 9 (10), art. no. e109630 |
الرقم المعياري الدولي للكتاب | 1932-6203 |
الملخص | 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. |
اللغة | en |
الناشر | Public Library of Science |
الموضوع | Autophagic cell death Apoptosis Breast cancer DNA damage Cell cycle and cell division Cancer treatment Mitochondria Reactive oxygen species |
النوع | Article |
رقم العدد | 10 |
رقم المجلد | 9 |
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