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


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KARABAY A. Z., KOÇ A., ÖZKAN T., Hekmatshoar Y., SUNGUROĞLU A., AKTAN F., ...More

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol.17, no.7, 2016 (SCI-Expanded, Scopus) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 17 Issue: 7
  • Publication Date: 2016
  • Doi Number: 10.3390/ijms17071123
  • Journal Name: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: MSM, HCT-116, apoptosis, Bim, colon cancer, JNK, ACTIVATED PROTEIN-KINASE, TUMOR-GROWTH, CYTOCHROME-C, BCL-2 FAMILY, JNK, PHOSPHORYLATION, PATHWAY, DEATH, BIM, PROLIFERATION
  • Open Archive Collection: AVESIS Open Access Collection
  • Ankara University Affiliated: Yes

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.