Methylsulfonylmethane suppresses hepatic tumor development through activation of apoptosis

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.

Metabolomic and transcriptomic profiling of hepatocellular carcinomas in Hras12V transgenic mice

“…Moreover, the hyperactivation of the MEK/ERK and PI3K/AKT/mTOR signaling pathways was a marked molecular event in HCC . Reports based on the Ras‐Tg mouse demonstrate that it is a valuable model to investigate molecular mechanisms, diagnosis and therapeutic strategies, and biomarkers of hepatocarcinogenesis . For example, by exploring Ras‐Tg mice, we found that differences in the molecular responses to the deregulated Ras oncoprotein between females and males determine the onset of HCC, which may contribute to the striking male prevalence of HCC .…”

Comparison of the Anti-tumor Effects of Selective Serotonin Reuptake Inhibitors as Well as Serotonin and Norepinephrine Reuptake Inhibitors in Human Hepatocellular Carcinoma Cells

“…33) A recent report suggested that sertraline induces apoptosis in HepG2 cells through the MAPK pathway. 15) Based on these reports, it is suggested that apoptosis through activation of the caspase pathway is involved in sertraline-induced toxicity in HepG2 cells.…”

Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement

“…This micronutrient is well tolerated for arthritis and a number of other conditions related to inflammation, physical function, and performance. Emerging research suggests that MSM may one day aid in the treatment of various types of cancer [49,99,100,101,119,120,121,122,123,125,126,181,184,185,186,194] or metabolic syndromes [195]. …”

“…In vitro studies indicate that MSM can induce apoptosis in gastrointestinal cancer cells [119], hepatic cancer cells [120], and colon cancer cells [121]. Contrary to these findings, MSM did not induce apoptosis in murine breast cancer cells [122].…”

“…In vitro studies using MSM alone or in combination have evaluated the metabolic and phenotypic effects of a number of cancer cell lines including breast [100,101,122,123,126,181], esophagus [119], stomach [119], liver [119,120], colon [121], bladder [99], and skin cancers [123,125] with promising results. MSM independently has been shown to be cytotoxic to cancer cells by inhibiting cell viability through the induction of cell cycle arrest [119,122,123], necrosis [119], or apoptosis [100,101,119,120,121]. The inhibition of cell growth and proliferation may be attributed to the metabolic alterations induced by MSM at the transcriptional and/or post-translational stages.…”