DECIPHERING THE MOLECULAR MECHANISM THROUGH WHICH RHUS CORIARIA EXERTS ITS ANTI-CANCER ACTIVITY

Cancer remains a major health problem around the globe. Among various types of treatments, plants have been shown to have great capacity in cancer treatment, one of which is Rhus coriaria. Commonly known as sumac, Rhus coriaria is a culinary herb that is known to possess different therapeutic values including anti-oxidant and anti-microbial activities. In this Ph.D. project, we tested the effect of Rhus coriaria extract (RCE) on the migration, invasion, and metastasis of MDA-MB-231 human breast cancer cells. We showed that non-cytotoxic concentrations of RCE inhibited migration and invasion, blocked adhesion to fibronectin, and downregulated MMP-9. Additionally, we found that RCE reduced VEGF production and downregulated the inflammatory cytokines TNF-α and IL-6. The suggested mechanism for the effect of RCE appears to be through inhibiting NFκB and STAT3 pathways. Moreover, we extended our study and investigated the anti-cancer effect of RCE on HT-29 and Caco-2 human colorectal cancer cells. We found that RCE inhibited the viability and colony growth of colon cancer cells. RCE also induced Beclin-1-independent autophagy and caspase-7- dependent apoptosis. The suggested mechanism through which RCE exerts its effect is by inactivating AKT/mTOR pathway and downregulating Beclin-1, p53, and procaspase- 3 through targeting them to proteasome-dependent degradation. Proteasome inhibition restored these proteins to a level comparable to control cells and reduced RCE-induced cell death and blocked the activation of autophagy and apoptosis. Proteasomal degradation of mTOR was concomitant with an overall increase in proteins ubiquitination which targets the proteins for degradation by the proteasome. In conclusion, these preliminary results make Rhus coriaria a promising therapeutic candidate against both breast and colorectal cancer