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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.
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.
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.
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 anti-proliferative and pro-apoptotic effects.
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.
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