Date of Award

4-2016

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Science

First Advisor

Dr. Rabah lratni

Second Advisor

Dr. Ranjit Vijayan

Third Advisor

Dr. Ahmed Murad

Abstract

Our lab has previously showed that carnosol, a naturally occurring polyphenol, exhibits anti-cancer activity by promoting cell cycle arrest at G2 phase, and induces reactive oxygen species (ROS) dependent apoptosis and beclin-1 independent autophagy in triple negative breast cancer (TNBC) cell line (MDA-MB-231). Here, we extended our study by investigating the potential effect of carnosol on migration, invasion and tumor growth of these cells. Our findings demonstrated that carnosol, at non-cytotoxic concentrations, exerted a potent anti-metastatic and anti-tumor growth activity against the highly invasive TNBC cell line, MBA-MB-231. Carnosol inhibited the migration and invasion of MDA-MB-231 cells. Moreover, carnosol suppressed the expression and activity of MMP-2 and MMP-9. Remarkably, our investigation revealed that TNF-α and STAT3 proteins that are involved in invasion and metastasis signaling were inhibited in MDA-MB-231 cells in response to carnosol. Furthermore, we demonstrated that carnosol significantly inhibited tumor growth and metastasis in vivo. In conclusion, our findings identify carnosol as a promising chemo preventive and chemotherapeutic candidate that modulate breast cancer growth and metastasis. Hence, carnosol deserves further study and exploration to identify its downstream mechanism(s) of action.

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