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المؤلفAl Dhaheri, Y.
المؤلفAttoub, S.
المؤلفRamadan, G.
المؤلفArafat, K.
المؤلفBajbouj, K.
المؤلفKaruvantevida, N.
المؤلفAbuQamar, S.
المؤلفEid, A.
المؤلفIratni, R.
تاريخ الإتاحة2016-02-08T14:21:26Z
تاريخ النشر2014-10
اسم المنشورPLoS ONE
المصدرScopus
الاقتباسAl 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 للكتاب1932-6203
معرّف المصادر الموحدhttp://dx.doi.org/10.1371/journal.pone.0109630
معرّف المصادر الموحدhttp://hdl.handle.net/10576/4126
الملخصBackground: 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.
اللغةen
الناشرPublic Library of Science
الموضوعAutophagic cell death
Apoptosis
Breast cancer
DNA damage
Cell cycle and cell division
Cancer treatment
Mitochondria
Reactive oxygen species
العنوانCarnosol induces ROS-mediated beclin1-independent autophagy and apoptosis in triple negative breast cancer
النوعArticle
رقم العدد10
رقم المجلد9
dc.accessType Open Access


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