Inhibition of Proliferation and Induction of Apoptosis by Gamma‐ or Delta‐Tocotrienols in Human Colorectal Carcinoma Cells

Colorectal cancer (CRC) remains a significant global health concern, necessitating the exploration of novel therapeutic approaches. This study investigated the anticancer effects of <i>γ</i>-tocotrienol (<i>γ</i>T3) and <i>δ</i>-tocotrienol (<i>δ</i>T3) on the human CRC cell lines HCC2998, HCT116, SW48 and Caco2. The cytotoxic effects were evaluated via cell viability assays, gene expression analysis and flow cytometry-based apoptosis detection. The results demonstrated that both <i>γ</i>T3 and <i>δ</i>T3 exhibited potent antiproliferative activities across all cell lines, with <i>δ</i>T3 generally showing lower IC₅₀ values. Gene expression analysis revealed cell line-specific responses, with HCT116 cells demonstrating significant upregulation of apoptosis-related genes, particularly in response to <i>γ</i>T3 treatment. Flow cytometry confirmed the apoptosis-inducing capabilities of both compounds, with effects intensifying from 24-48 h of treatment. The response of HCT116 cells was the most pronounced, especially in response to <i>δ</i>T3 treatment. Both <i>γ</i>T3 and <i>δ</i>T3, after 48 h of treatment, induced significant G₁ phase cell cycle arrest in HCC2998 cells, with <i>δ</i>T3 exhibiting a more pronounced suppression of S phase progression. These findings contribute to the growing evidence supporting the potential of T3 as a therapeutic agent for CRC, highlighting its ability to inhibit proliferation and induce apoptosis in multiple CRC cell lines. Further research is warranted to elucidate the precise mechanisms of action and evaluate the in vivo efficacy of these compounds.