Selenium-Enriched Rapeseed Extract Synergizes with Chemotherapy Drug Cisplatin in Inhibiting Proliferation and Promoting Apoptosis of Colorectal Cancer Cells

Chemotherapy treatment of colorectal cancer (CRC) with cisplatin (CDDP) faces drug resistance and cytotoxicity issues, highlighting the urgent need for combination strategies. Selenium-enriched rapeseed extracts exhibit anticancer effects; however, their bioactive components and mechanisms remain unclear. Here, we applied different solvents to fractionate extracts of selenium-enriched rapeseed and found that the water extract (WE) fraction significantly enhanced the cytotoxic effect of CDDP on cancer cells without damaging normal cells, namely, HK-2 and NCM460. High-performance liquid chromatography–inductively coupled plasma–mass spectrometry (HPLC-ICP-MS) analysis revealed methylselenocysteine (MSC) and selenocysteine (SeCys2) as the main selenium species in the WE. Through cell biology and integrative multi-omics analysis, we found a synergistic anti-CRC cell effect upon combining CDDP with MSC, sulforaphane (SFN), celastrol (Cel), indole-3-carbinol (I3C), α-linolenic acid (ALA) or linoleic acid (LA). We propose that CDDP-WE (cisplatin and water extract) combination treatment holds promise for improving antitumor efficacy against chemo-refractory cells.