Interleukin-17F suppressed colon cancer by enhancing caspase 4 mediated pyroptosis of endothelial cells.

The combination of anti-angiogenic treatment and immunotherapy presents a promising strategy against colon cancer. Interleukin-17F (IL-17F) emerges as a critical immune cell cytokine expressed in colonic epithelial cells, demonstrating potential in inhibiting angiogenesis. In order to clarify the roles of IL-17F in the colon cancer microenvironment and elucidate its mechanism, we established a mouse colon carcinoma cell line CT26 overexpressing IL-17F and transplanted it subcutaneously into syngeneic BALB/c mice. We also analyzed induced colon tumor in IL-17F knockout and wild type mice. Our results demonstrated that IL-17F could suppress colon tumor growth in vivo with inhibited angiogenesis and enhanced recruitment of cysteine-cysteine motif chemokine receptor 6 (CCR6) positive immune cells. Additionally, IL-17F suppressed the tube formation, cell growth and migration of endothelial cells EOMA in vitro. Comprehensive bioinformatics analysis of transcriptome profiles between EOMA cells and those treated with three different concentrations of IL-17F identified 109 differentially expressed genes. Notably, a potential new target, Caspase 4, showed increased expressions after IL-17F treatment in endothelial cells. Further molecular validation revealed a novel downstream signaling for IL-17F: IL-17F enhanced Caspase 4/GSDMD signaling of endothelial cells, CT26 cells and CT26 transplanted tumors, while IL-17F knockout colon tumors exhibited decreased Caspase 4/GSDMD signaling. The heightened expression of the GSDMD N-terminus, coupled with increased cellular propidium iodide (PI) uptake and lactate dehydrogenase (LDH) release, revealed that IL-17F promoted pyroptosis of endothelial cells. Altogether, IL-17F could modulate the colon tumor microenvironment with inhibited angiogenesis, underscoring its potential as a therapeutic target for colon cancer.

Lycopene suppresses gastric cancer cell growth without affecting normal gastric epithelial cells.

Gastric cancer is one of the leading causes of cancer-related death worldwide. Lycopene, a natural carotenoid, has potent antioxidant activity and anti-cancer effects against several types of cancers. However, the mechanism for the anti-gastric cancer effects of lycopene remains to be fully clarified. Normal gastric epithelial cell line GES-1 and gastric cancer cell line AGS, SGC-7901, Hs746T cells were treated with different concentrations of lycopene and the effects of lycopene were compared. Lycopene specifically suppressed cell growth monitored by Real-Time Cell Analyzer, induced cell cycle arrest and cell apoptosis detected by flow cytometry, and lowered mitochondrial membrane potentials assessed by JC-1 staining of AGS and SGC-7901 cells, while did not affect those of GES-1 cells. Lycopene did not affect the cell growth of Hs746T cells harboring TP53 mutation. Further bioinformatics analysis predicted 57 genes with up-regulated expression levels in gastric cancer and decreased function in cells after lycopene treatment. Quantitative PCR and Western Blot were used to check the critical factors in the cell cycle and apoptosis signaling pathway. Lycopene decreased the high expression levels of CCNE1 and increased the levels of TP53 in AGS and SGC-7901 cells without affecting those in GES-1 cells. In summary, lycopene could effectively suppress gastric cancer cells with CCNE1-amplification, which could be a promising target therapy reagent for gastric cancer.