Brief Article
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World J Hepatol. Feb 27, 2014; 6(2): 98-106
Published online Feb 27, 2014. doi: 10.4254/wjh.v6.i2.98
Methylsulfonylmethane suppresses hepatic tumor development through activation of apoptosis
Joo-Hyun Kim, Hye-Jun Shin, Hye-Lin Ha, Young-Ho Park, Tae-Ho Kwon, Mi-Ra Jung, Hyung-Bae Moon, Eun-Sang Cho, Hwa-Young Son, Dae-Yeul Yu
Joo-Hyun Kim, Hye-Jun Shin, Hye-Lin Ha, Young-Ho Park, Tae-Ho Kwon, Mi-Ra Jung, Dae-Yeul Yu, Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea
Hyung-Bae Moon, Wonkwang University College of Medicine, Iksan 570-749, South Korea
Joo-Hyun Kim, Eun-Sang Cho, Hwa-Young Son, College of Veterinary Medicine, Chungnam National University, Daejeon 305-764, South Korea
Author contributions: Kim JH, Ha HL, Son HY and Yu DY planned the experiments and analyses; Kim JH, Ha HL, Shin HJ, Park YH, Kwon TH, Jung MR, Moon HB, Cho ES, Son HY and Yu DY performed the experiments and analyzed the results; Kim JH and Yu DY wrote the manuscript; all the authors discussed the results and commented on the manuscript.
Supported by The World Class Institute (WCI) Program of the National Research Foundation of Korea (NRF), No. WCM0101222; Ministry of Education, Science and Technology of Korea (MEST), the National R and D Program for Cancer Control, Ministry of Health and Welfare, South Korea, No. BCM0061213; KRIBB Research Initiative Program Grant, No. KGM3141312
Correspondence to: Dae-Yeul Yu, PhD, Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, South Korea.
Telephone: +82-42-8604422 Fax: +82-42-8604609
Received: August 29, 2013
Revised: December 2, 2013
Accepted: December 12, 2013
Published online: February 27, 2014

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-rasG12V, 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-ras12V transgenic mice for 3 mo.

RESULTS: MSM decreased the growth of HepG2, Huh7-Mock and Huh7-H-rasG12V 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-ras12V 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: Methylsulfonylmethane, Anti-cancer effects, Liver cancer cells, Transgenic mice, Hepatic tumorigenesis

Core tip: Methylsulfonylmethane (MSM) is an organic sulfur-containing compound. MSM suppressed hepatic tumor growth through activation of apoptosis. MSM could be a potential candidate as an anti-liver cancer agent.