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Volume 10 Journal of Cancer Science & Therapy
ISSN: 1948-5956 Euro Cancer 2018
July 23-25, 2018
July 23-25, 2018 | Rome, Italy
29th Euro-Global Summit on
Cancer Therapy & Radiation Oncology
Targeting the AKT/mTOR/STAT3 pathways through a ROS-dependent ubiquitin proteasome
degradation in breast cancer by the natural polyphenol compound, carnosol
Rabah Iratni, Hussain El Hasasna and Halima Al Samri
United Arab Emirates University, UAE
We have previously showed that carnosol significantly inhibited the viability and colony growth of triple negative breast
cancer cells and induced ROS-dependent beclin-1-independent autophagy and subsequent apoptotic cell death. Here
were analyzed the molecular mechanism through which carnosol exerts its anti-cancer activity. Mechanistically, we found
that carnosol inactivated the AKT/mTOR pathway by promoting the proteasome-dependent degradation of both proteins.
Strikingly, we also found that carnosol targets Stat3 to degradation. Proteasome inhibition restored these proteins to a level
comparable to control cells. The proteasomal degradation of mTOR, which occurred as early as 30 minutes post- carnosol
treatment was concomitant with an overall increase in the level of ubiquitinated proteins and translated stimulation of
proteolysis by the proteasome. Interestingly, we found that the treatment of the breast cancer cells with N-acetylcysteine,
an ROS inhibitor, not only restored AKT/mTOR/Stat3 proteins to a level comparable to control cells, but also dramatically
reduced carnosol-induced cell death and blocked the activation of autophagy and apoptosis. Our findings demonstrate that
carnosol exerts its anti-breast cancer activity through stimulation ubiquitin proteasome system which consequently triggers
both autophagy and apoptosis, making it a potential and valuable source of novel therapeutic cancer drug.
Biography
Rabah Iratni completed his PhD in Cellular and Molecular Biology from the University Joseph Fourier Grenoble 1 (France) and Post-doctorate from the University of
Medicine and Dentistry of New Jersey (USA). He is currently a Professor at the United Arab Emirates University. His lab focuses on the discovery of new biologically active
natural products, to evaluate their potential as therapeutic agents against breast cancer and determine their mechanism(s) of action. He also has a strong interest in the
understanding of the epigenetic basis of cancer with focus on breast cancer. He has authored several papers in prestigious journals including Cell, Science, Molecular
Cell, Genes & Development, PNAS, etc.
Rabah Iratni et al., J Cancer Sci Ther 2018, Volume 10
DOI: 10.4172/1948-5956-C8-144