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. 2014 Feb 27;6(2):98-106.
doi: 10.4254/wjh.v6.i2.98.

Methylsulfonylmethane suppresses hepatic tumor development through activation of apoptosis

Joo-Hyun Kim  1 , Hye-Jun Shin  1 , Hye-Lin Ha  1 , Young-Ho Park  1 , Tae-Ho Kwon  1 , Mi-Ra Jung  1 , Hyung-Bae Moon  1 , Eun-Sang Cho  1 , Hwa-Young Son  1 , Dae-Yeul Yu  1
Affiliations

Methylsulfonylmethane suppresses hepatic tumor development through activation of apoptosis

Joo-Hyun Kim et al. World J Hepatol. .

Abstract

Aim: To investigate the effect of methylsulfonylmethane (MSM), recently reported to have anti-cancer effects, in liver cancer cells and transgenic mice.

Methods: Three liver cancer cell lines, HepG2, Huh7-Mock and Huh7-H-ras (G12V), were used. Cell growth was measured by Cell Counting Kit-8 and soft agar assay. Western blot analysis was used to detect caspases, poly (ADP-ribose) polymerase (PARP), and B-cell lymphoma 2 (Bcl-2) expressions. For in vivo study, we administered MSM to H-ras (12V) transgenic mice for 3 mo.

Results: MSM decreased the growth of HepG2, Huh7-Mock and Huh7-H-ras (G12V) cells in a dose-dependent manner. That was correlated with significantly increased apoptosis and reduced cell numbers in MSM treated cells. Cleaved caspase-8, cleaved caspase-3 and cleaved PARP were remarkably increased in the liver cancer cells treated with 500 mmol/L of MSM; however, Bcl-2 was slightly decreased in 500 mmol/L. Liver tumor development was greatly inhibited in the H-ras (12V) transgenic mice treated with MSM, compared to control, by showing reduced tumor size and number. Cleaved PARP was significantly increased in non-tumor treated with MSM compared to control.

Conclusion: Liver injury was also significantly attenuated in the mice treated with MSM. Taken together, all the results suggest that MSM has anti-cancer effects through inducing apoptosis in liver cancer.

Keywords: Anti-cancer effects; Hepatic tumorigenesis; Liver cancer cells; Methylsulfonylmethane; Transgenic mice.

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Figures

Figure 1
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
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-rasG12V cell line for 24 h. bP < 0.001 vs control. MSM: Methylsulfonylmethane.
Figure 3
Figure 3
Methylsulfonylmethane increases caspase-3, -8 and PARP activation in liver cancer cell lines. A: Expression levels of HA-H-rasG12V in Huh7-H-rasG12V; 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
Figure 4
Methylsulfonylmethane inhibits hepatic tumorigenesis in H-ras12V transgenic mice. H-ras12V 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-ras12V transgenic mice (Scale bars, 500 μm); C: Expression levels of cleaved PARP in H-ras12V livers; D: The levels of AST and ALT in plasma of H-ras12V transgenic mice treated with MSM. MSM: Methylsulfonylmethane; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.
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