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Int. J. Mol. Sci. 2016, 17(7), 1123;

Methylsulfonylmethane Induces p53 Independent Apoptosis in HCT-116 Colon Cancer Cells

Faculty of Pharmacy, Department of Biochemistry, Ankara University, 06100 Ankara, Turkey
Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey
Faculty of Medicine, Department of Medical Biology, Ankara University, 06560 Ankara, Turkey
Authors to whom correspondence should be addressed.
Academic Editor: Atsushi Matsuzawa
Received: 11 March 2016 / Revised: 30 June 2016 / Accepted: 6 July 2016 / Published: 15 July 2016
(This article belongs to the Special Issue Kinase Signal Transduction)
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Methylsulfonylmethane (MSM) is an organic sulfur-containing compound which has been used as a dietary supplement for osteoarthritis. MSM has been shown to reduce oxidative stress and inflammation, as well as exhibit apoptotic or anti-apoptotic effects depending on the cell type or activating stimuli. However, there are still a lot of unknowns about the mechanisms of actions of MSM. In this study, MSM was tested on colon cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis revealed that MSM inhibited cell viability and increased apoptotic markers in both HCT-116 p53 +/+ and HCT-116 p53 −/− colon cancer cells. Increased poly (ADP-ribose) polymerase (PARP) fragmentation and caspase-3 activity by MSM also supported these findings. MSM also modulated the expression of various apoptosis-related genes and proteins. Moreover, MSM was found to increase c-Jun N-terminal kinases (JNK) phosphorylation in both cell lines, dose-dependently. In conclusion, our results show for the first time that MSM induces apoptosis in HCT-116 colon cancer cells regardless of their p53 status. Since p53 is defective in >50% of tumors, the ability of MSM to induce apoptosis independently of p53 may offer an advantage in anti-tumor therapy. Moreover, the remarkable effect of MSM on Bim, an apoptotic protein, also suggests its potential use as a novel chemotherapeutic agent for Bim-targeted anti-cancer therapies. View Full-Text
Keywords: MSM; HCT-116; apoptosis; Bim; colon cancer; JNK MSM; HCT-116; apoptosis; Bim; colon cancer; JNK

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Karabay, A.Z.; Koc, A.; Ozkan, T.; Hekmatshoar, Y.; Sunguroglu, A.; Aktan, F.; Buyukbingol, Z. Methylsulfonylmethane Induces p53 Independent Apoptosis in HCT-116 Colon Cancer Cells. Int. J. Mol. Sci. 2016, 17, 1123.

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