Format

Send to

Choose Destination
Int J Mol Sci. 2016 Jul 15;17(7). pii: E1123. doi: 10.3390/ijms17071123.

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

Author information

1
Faculty of Pharmacy, Department of Biochemistry, Ankara University, 06100 Ankara, Turkey. akarabay@ankara.edu.tr.
2
Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey. akoc@ankara.edu.tr.
3
Faculty of Medicine, Department of Medical Biology, Ankara University, 06560 Ankara, Turkey. tozkan@ankara.edu.tr.
4
Faculty of Medicine, Department of Medical Biology, Ankara University, 06560 Ankara, Turkey. yaldahekmatshoar@yahoo.com.
5
Faculty of Medicine, Department of Medical Biology, Ankara University, 06560 Ankara, Turkey. asungur@medicine.ankara.edu.tr.
6
Faculty of Pharmacy, Department of Biochemistry, Ankara University, 06100 Ankara, Turkey. aktanf@ankara.edu.tr.
7
Faculty of Pharmacy, Department of Biochemistry, Ankara University, 06100 Ankara, Turkey. zbuyukbingol@ankara.edu.tr.

Abstract

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.

KEYWORDS:

Bim; HCT-116; JNK; MSM; apoptosis; colon cancer

PMID:
27428957
PMCID:
PMC4964498
DOI:
10.3390/ijms17071123
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center