title: Methylsulfonylmethane Induces G1Arrest and Mitochondrial Apoptosis in YD-38 Gingival Cancer Cells.
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/Cip1and P27Kip1genes 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.
authors.affiliation: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Nipin S
authors.initials: NS
authors.lastname: P
authors.affiliation: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Dong Young
authors.initials: DY
authors.lastname: Kang
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Baek Joong
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Youn Hee
authors.initials: YH
authors.lastname: Joung
authors.affiliation: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Pramod
authors.initials: P
authors.lastname: Darvin
authors.affiliation: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Hyo Joo
authors.initials: HJ
authors.lastname: Byun
authors.affiliation: Natural & Inc. Bando officetel, Busan, Republic of Korea.
authors.forename: Joong Gon
authors.initials: JG
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Je Uk
authors.initials: JU
authors.lastname: Park
authors.affiliation: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea ymyang@kku.ac.kr.
authors.forename: Young Mok
authors.initials: YM
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D005887:Gingival Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D013450:Sulfones; D045304:Cytochromes c; C025910:dimethyl sulfone; D011065:Poly(ADP-ribose) Polymerases; D004121:Dimethyl Sulfoxide
keywords: BAX-BCL-2; CYC; G1 arrest; MSM; mitochondrial apoptosis