Methylsulfonylmethane Induces G1 Arrest and Mitochondrial Apoptosis in YD-38 Gingival Cancer Cells

Anticancer Res. 2017 Apr;37(4):1637-1646. doi: 10.21873/anticanres.11494.

Abstract

Gingival squamous cell carcinoma is a rare form of cancer that accounts for less than 10% of all head and neck cancers. Targeted therapies with natural compounds are of interest because they possess high efficacy with fewer side-effects. Methylsulfonylmethane (MSM) is an organic sulfur-containing compound with anticancer activities. The main goal of this study was to induce proliferation inhibition and apoptosis in the metastatic YD-38 cell line. MSM up-regulated expression of P21Waf1/Cip1 and P27Kip1 genes and down-regulated expression of cyclin D1 (CCND1) and CDK4. Moreover, treatment with MSM induced apoptosis and up-regulation of BAX in YD-38 cells. In accordance, the expression of the BCL-2 and BCL-XL, were inhibited, indicating the role of mitochondria in MSM-induced apoptosis. Analysis of mitochondrial integrity showed a loss of mitochondrial potential with an increased level of cytochrome c in the cytosol compared to mitochondria. Active CASPASE-3 (CASP3) was also observed, confirming that MSM-induced apoptosis is caspase-mediated.

Keywords: BAX-BCL-2; CYC; G1 arrest; MSM; mitochondrial apoptosis.

MeSH terms

  • Apoptosis / drug effects
  • Blotting, Western
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cytochromes c / metabolism
  • Dimethyl Sulfoxide / pharmacology*
  • G1 Phase / drug effects*
  • Gingival Neoplasms / drug therapy
  • Gingival Neoplasms / metabolism
  • Gingival Neoplasms / pathology*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Sulfones / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Messenger
  • Sulfones
  • Cytochromes c
  • dimethyl sulfone
  • Poly(ADP-ribose) Polymerases
  • Dimethyl Sulfoxide