Exploring the Therapeutic Potential of Ferula assa-foetida Oleo-gum-resin in Colon Cancer: Emerging Links to Immunotherapy

Introduction: Colorectal cancer (CRC) ranks among the top global malignancies, with limited treatment options for advanced, microsatellite-stable (MSS) tumors resistant to immunotherapy. Ferula assa-foetida oleo-gum-resin, a traditional medicinal plant from Iran, exhibits promising anti-cancer and immunomodulatory properties. This study investigates its effects on HCT-116 CRC cells, focusing on cytotoxicity, apoptosis, and potential synergy with immunotherapy via PD-L1 modulation. Methods: Oleo-gum-resin extract from authenticated Ferula assa-foetida was applied to HCT- 116 cells at 0.1–1000 μg/mL for 24, 48, and 72 hours. Cell viability was measured using the MTT assay. mRNA expression of Mina53, IGF1, PD-L1, Bcl-2, BAX, Caspase-3, VEGF, and VEGFR was quantified by real-time PCR. Statistical analysis employed ANOVA with Tukey- Kramer post hoc tests. Results: Asafoetida induced dose- and time-dependent cytotoxicity, reducing cell viability to 5% at 1000 μg/mL by 72 hours (P <0.01). It significantly downregulated Mina53, IGF1, PD-L1, Bcl-2, VEGF, and VEGFR, while upregulating pro-apoptotic BAX and Caspase-3 (P <0.01), indicating inhibited proliferation, angiogenesis, and immune evasion, alongside apoptosis induction. Discussion: Asafoetida bioactive compounds, including ferulic acid, likely suppress oncogenic pathways and enhance immune surveillance by reducing PD-L1 expression, potentially complementing immunotherapy for MSS CRC. These findings align with prior studies on its antiproliferative and pro-apoptotic effects. Conclusion: Ferula assa-foetida shows potent anti-cancer effects against HCT-116 cells, with PD-L1 suppression suggesting immunotherapy synergy. Further in vivo and clinical studies are needed to confirm its therapeutic role in CRC.