Evaluation of the Leaves and Seeds of Cucurbitaceae Plants as a New Source of Bioactive Compounds for Colorectal Cancer Prevention and Treatment.

BACKGROUND/OBJECTIVES: The Cucurbitaceae family represents an important source of bioactive compounds with antioxidant, antimicrobial, anti-inflammatory and antitumor activities. This study aims to investigate the potential application of Cucurbitaceae leaves and seed extracts to prevent and treat colorectal cancer (CRC). METHODS: Four extracts (ethanol extracts and protein extracts and hydrolysates) from the leaves and seeds of cucurbits were tested in T-84, HCT-15 and HT-29 CRC cells. The antitumor, antiangiogenic, antioxidant and chemopreventive potentials and bioactive composition of the active extracts were characterized. RESULTS: Cold ethanolic extracts from the leaves and seeds of two interspecific Cucurbita genera (CLU01002 and COK01001) exhibited potent antiproliferative, specific and non-hepatotoxic activity against CRC cell lines, with a slight synergistic effect in combination with oxaliplatin. This antitumor activity was related to G(2)/M cell cycle arrest, the extrinsic apoptosis pathway, cytokinesis inhibition and autophagy. The extracts also inhibited tumor clonogenicity and angiogenesis, and modulated cancer stem cell (CSC) gene expression, as well as expressing antioxidant and chemopreventive cellular capabilities. Finally, phenolic and cucurbitane-type triterpenoid compounds (pengxianencins and cucurbitacins) were tentatively identified in the active extracts by UPLC-MS analysis and bioguided fractionation. CONCLUSIONS: Extracts from leaves the and seeds of two interspecific Cucurbita genera (CLU01002 and COK01001) may contribute to the improvement of prevention and treatment strategies for CRC patients.