Carob leaf polyphenols trigger intrinsic apoptotic pathway and induce cell cycle arrest in colon cancer cells

Abstract

Chemoprevention of Colorectal cancer (CRC) is the major concern for improving public health. We investigated the protective effects of carob, Ceratonia siliqua L., leaf polyphenols (CLP) against CRC. Phenolic content analysis showed that CLP is enriched with gallic acid and m-coumaric acid. We observed that CLP exerted a dose dependent cytotoxic effect through the induction of apoptosis on CRC cell lines, with an IC50 around 20 μg/mL. CLP induced intrinsic apoptotic pathway through the caspase-9 activation and PARP cleavage in HCT-116 and CT-26 cells. Moreover, CLP induced cell cycle arrest in the G1 phase through p53 activation. Gallic acid and m-coumaric acid exerted similar effect of CLP but at higher concentration to that expected to be present in CLP, suggesting the synergistic effect between polyphenols in CLP activity. Interestingly, the carob leaf infusion reduced CT-26 tumour growth in BALB/c mice. This study suggests that CLP can be used for the prevention of CRC.

Keywords

• Carob (Ceratonia siliqua L.)
• Polyphenols
• Colorectal cancer
• Caspases
• Apoptosis
• Cell cycle arrest