Male infertility, a global health issue marked by spermatogenic failure, hinges on selenium (Se) as a key element for normal spermatogenesis. Among different Se species, Se-methylselenocysteine (MeSeCys) has been developed as a natural organic Se supplement with potent antioxidant and anti-inflammatory properties, but its direct effects on male reproduction need to be further explored. This study investigated the effect of MeSeCys on GC-1 spg (GC-1) and GC-2 spd (ts) (GC-2) cell lines, which mimic early stages. Treatment with 75 μmol/L MeSeCys for 24 h markedly enhanced the viability of both cell lines, with a more pronounced effect observed in GC-1 than in GC-2 cells. Moreover, this study demonstrated that MeSeCys enters cells through SLC7A11 or LRP8 channels and elevates intracellular Se levels in both GC-1 and GC-2 cells, with higher levels observed in GC-1 cells. RNA sequencing (RNA-seq) and bioinformatics analysis revealed that MeSeCys may regulate selenocompound metabolism and the glutathione metabolism pathway in both cell lines, increasing their intracellular glutathione (GSH) levels. Importantly, in GC-1 cells, MeSeCys specifically modulates the mTOR pathway, which further modulates glutathione metabolism and intracellular redox balance. This finding provides novel insights into the beneficial effects of MeSeCys on male reproductive cells, highlighting its potential as a nutritional supplement for male reproductive health.

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.