Chlorophyllin attenuates the effects of benzo[a]pyrene in human hepatoma HepG2/C3A cells

Abstract

Abstract Chlorophyllin (Chl), a semisynthetic compound derived from chlorophyll, has been a focus in cancer prevention because it exerts important biological activities, such as antigenotoxic, antioxidative and anticarcinogenic activities. Given that most sporadic cancers are related to environmental chemicals exposure and based on evidence that Chl has the ability to protect cells against carcinogenic effects of these compounds, the aim of this study was to evaluate the protective effect of Chl against benzo[a]pyrene toxicity in HepG2/C3A cells. To investigate the ability of Chl to mitigate the cytotoxic effects of B[a]P, the cells were co-treated and the cell viability, cell growth kinetics, cell cycle, and apoptosis induction were evaluated. Besides, the mRNA levels of cell cycle components (cyclins and cyclin-dependent kinases - CDKs) and apoptotic genes were analyzed. Our results showed that Chl was able to reduce the cytotoxic and antiproliferative effects of B[a]P in a multi-specific manner, restoring the normal distribution of the cell cycle and inhibiting the cell death induced by the xenobiotic. The RT-qPCR analysis showed that Chl caused a downregulation in cyclin CCNA2 and cyclin-dependent kinases CDK1 and CDK2 mRNA level. B[a]P decreased the mRNA levels of genes involved in cell cycle control (CCNA2, CCNB1, CCND1 and CCNE1 cyclins; and CDK1 and CDK2 cyclin-dependent kinases) and apoptosis (BAX, CASP7, and TP53). Cells co-treated with 200 µM Chl and B[a]P also showed a downregulation of mRNA levels of the genes. Chl maintained the TP53 gene expression in B[a]P-treated cells near control levels. Thus, Chl is a good candidate as a chemoprotective agent that mitigates the cytotoxic effects B[a]P and, thus, might be a promising tool to prevent liver cancer.