Valorization of Purple Prickly Pear Peel By‐Products: Antiproliferative and Pro‐Apoptotic Effects on Human Colorectal Cancer Cells HCT116

Opuntia fcus-indica peel is known to possess antioxidant, anti-infammatory, and anticancer activities and currently is discarded orused for animal feeding. Within this context, the aim of this work was to evaluate the antiproliferative and pro-apoptotic efect ofpurple prickly pear peel extract (PPE) on the human colon adenocarcinoma cancer cell line (HTC116). The methanolic extract of PPEwas characterized in terms of betalain and polyphenols as well as total antioxidant capacity. Cell viability, apoptosis induction, cellcycle arrest, and reactive oxygen species (ROS) production assays were performed. Important proteins and genes related to pro-liferation and apoptosis were determined. PPE represents a good source of bioactive compounds with a high antioxidant capacity. Cellviability was reduced gradually by PPE treatments, with lower efects in nontumorigenic cells. Compared to the control group,a signifcant induction of apoptosis as well as cell cycle arrest in the sub-G1 phase and ROS production was observed in PPE-treatedcells. Furthermore, the treatment induced the overexpression of p53 at protein levels and upregulated the mRNA expression of pro-apoptotic BAX, CASP9, BID, and CYCS, along with the signifcant decrease of anti-apoptotic BCL2 gene expression. Simultaneously,cyclin D1 and CDK4 gene expression were signifcantly decreased, while p21 increased considerably. The treatment also induced thedownregulation of Her2 and PI3K at protein levels and caused the suppression of PI3KCA and mTOR expression at gene levels.Overall, these fndings suggested that PPE has potential anticancer efects against human colon adenocarcinoma progression.