Methylsulfonylmethane suppresses hepatic tumor development through activation of apoptosis

Figure 1 Inhibitory effect of methylsulfonylmethane in liver cancer cell lines. A: Cellular proliferation effects of MSM were measured by CCK-8 assay. Cells were treated with MSM (0, 200 μmol/L, 200 mmol/L, and 500 mmol/L) at different time points (0, 24, 48, 72 and 96 h); B: Anchorage-independent growth assay was performed in liver cancer cells treated with MSM in a dose-dependent manner. ^bP < 0.001 vs control. MSM: Methylsulfonylmethane.

Figure 2 Methylsulfonylmethane induces apoptosis in liver cancer cell lines. A: Detection of apoptotic cells by Annexin V. Cells were treated with MSM in a dose-dependent manner for 24 h; B: Dose-dependent effects of MSM on the morphology and live cell counting of Huh7-H-ras^G12V cell line for 24 h. ^bP < 0.001 vs control. MSM: Methylsulfonylmethane.

Figure 3 Methylsulfonylmethane increases caspase-3, -8 and PARP activation in liver cancer cell lines. A: Expression levels of HA-H-ras^G12V in Huh7-H-ras^G12V; B: Expression levels of cleaved caspase-3, cleaved caspase-8 and cleaved PARP in liver cancer cells were determined by Western blotting analysis. Cells were treated with MSM in a dose-dependent manner for 24 h; C: Expression of Bcl-2 in liver cancer cells treated with MSM in a dose-dependent manner for 24 h. Numbers under each result indicate a fold increase of band density as compared to control, GAPDH. MSM: Methylsulfonylmethane; PARP: Poly (ADP-ribose) polymerase.

Figure 4 Methylsulfonylmethane inhibits hepatic tumorigenesis in H-ras^12V transgenic mice. H-ras^12V transgenic mice were administered with PBS and MSM (100 μg/g) every day for 3 mo. A: Liver morphologies of PBS (control) group (left) and MSM group (right) after administration for 3 mo; B: Hematoxylin and eosin stained section in livers of PBS and MSM treated H-ras^12V transgenic mice (Scale bars, 500 μm); C: Expression levels of cleaved PARP in H-ras^12V livers; D: The levels of AST and ALT in plasma of H-ras^12V transgenic mice treated with MSM. MSM: Methylsulfonylmethane; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.