title: Methylsulfonylmethane Induces p53 Independent Apoptosis in HCT-116 Colon Cancer Cells.
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.
authors.affiliation: Faculty of Pharmacy, Department of Biochemistry, Ankara University, 06100 Ankara, Turkey. akarabay@ankara.edu.tr.
authors.forename: Arzu Zeynep
authors.initials: AZ
authors.lastname: Karabay
authors.affiliation: Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey. akoc@ankara.edu.tr.
authors.forename: Asli
authors.initials: A
authors.lastname: Koc
authors.affiliation: Faculty of Medicine, Department of Medical Biology, Ankara University, 06560 Ankara, Turkey. tozkan@ankara.edu.tr.
authors.forename: Tulin
authors.initials: T
authors.lastname: Ozkan
authors.affiliation: Faculty of Medicine, Department of Medical Biology, Ankara University, 06560 Ankara, Turkey. yaldahekmatshoar@yahoo.com.
authors.forename: Yalda
authors.initials: Y
authors.lastname: Hekmatshoar
authors.affiliation: Faculty of Medicine, Department of Medical Biology, Ankara University, 06560 Ankara, Turkey. asungur@medicine.ankara.edu.tr.
authors.forename: Asuman
authors.initials: A
authors.lastname: Sunguroglu
authors.affiliation: Faculty of Pharmacy, Department of Biochemistry, Ankara University, 06100 Ankara, Turkey. aktanf@ankara.edu.tr.
authors.forename: Fugen
authors.initials: F
authors.lastname: Aktan
authors.affiliation: Faculty of Pharmacy, Department of Biochemistry, Ankara University, 06100 Ankara, Turkey. zbuyukbingol@ankara.edu.tr.
authors.forename: Zeliha
authors.initials: Z
authors.lastname: Buyukbingol
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D008856:Microscopy, Fluorescence; D060888:Real-Time Polymerase Chain Reaction; D013450:Sulfones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D013450:Sulfones; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C025910:dimethyl sulfone; D004121:Dimethyl Sulfoxide
keywords: Bim; HCT-116; JNK; MSM; apoptosis; colon cancer