Targeting apoptosis via inactivation of PI3K/Akt/mTOR signaling pathway involving NF-κB by geraniin in HT-29 human colorectal adenocarcinoma cells

Abstract

Dietary phytochemicals possess a variety of biological activities which can be widely discovered in fruits, vegetables and herbs. Geraniin, an ellagitannin is commonly found in fruits and herbs which possesses multitude of health benefits including anti-diabetic, hepatoprotective, anti-inflammatory and anticancer. However, the effects of geraniin on human colorectal adenocarcinoma cells have yet to be evaluated. This study aimed to investigate the apoptotic effects of geraniin against selected human cancer cell lines and elucidate its underlying mechanisms. Geraniin exhibited the strongest cytotoxic effect on HT-29 cells as determined by MTT assay. Events of apoptosis induced by geraniin in HT-29 cells was portrayed by apoptotic morphological changes, externalization of phosphatidylserine, DNA fragmentation and dissipation of mitochondrial membrane potential. Western blot analysis was then used to investigate the mechanisms underlying observed growth inhibition. Geraniin was found to initiate p53 activation further resulting in elevation of Bak/Bcl-xL ratio and caspase-3 activation. This eventually led to HT-29 cell death via apoptosis. Additionally, exposure of geraniin on HT-29 cells found to suppress the PI3K/Akt/mTOR pathway and suppression of NF-kB. Cumulative evidences in this study suggests that geraniin inhibited colorectal adenocarcinoma cell proliferation via apoptosis induction and suppression of PI3K/Akt/mTOR pathway. Thus, these findings provide novel mechanistic insight for the therapeutic potential of geraniin in the treatment of colorectal adenocarcinoma.