Sulforaphane, a Dietary Isothiocyanate, Induces G₂/M Arrest in Cervical Cancer Cells through CyclinB1 Downregulation and GADD45β/CDC2 Association.
Globally, cervical cancer is the most common malignancy affecting women. The main treatment methods for this type of cancer include conization or hysterectomy procedures. Sulforaphane (SFN) is a natural, compound-based drug derived from dietary isothiocyanates which has previously been shown to possess potent anti-tumor and chemopreventive effects against several types of cancer. The present study investigated the effects of SFN on anti-proliferation and G₂/M phase cell cycle arrest in cervical cancer cell lines (Cx, CxWJ, and HeLa). We found that cytotoxicity is associated with an accumulation of cells in the G₂/M phases of the cell-cycle. Treatment with SFN led to cell cycle arrest as well as the down-regulation of Cyclin B1 expression, but not of CDC2 expression. In addition, the effects of GADD45β gene activation in cell cycle arrest increase proportionally with the dose of SFN; however, mitotic delay and the inhibition of proliferation both depend on the dosage of SFN used to treat cancer cells. These results indicate that SFN may delay the development of cancer by arresting cell growth in the G₂/M phase via down-regulation of Cyclin B1 gene expression, dissociation of the cyclin B1/CDC2 complex, and up-regulation of GADD45β proteins.
Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan. chengym@mail.ncku.edu.tw.|Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan. chengym@mail.ncku.edu.tw.
Ya-Min
YM
Cheng
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan. nick@cgmh.org.tw.|Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Chiayi 61333, Taiwan. nick@cgmh.org.tw.
Ching-Chou
CC
Tsai
Graduate Institute of Medical Science, College of Health Sciences, Chang Jung Christian University, Tainan 71101, Taiwan. d8702008@tmu.edu.tw.|Bachelor Degree Program of Medical Sciences Industry, College of Health Sciences, Chang Jung Christian University, Tainan 71101, Taiwan. d8702008@tmu.edu.tw.
Yi-Chiang
YC
Hsu
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000943:Antigens, Differentiation / Q000235:genetics; D016203:CDC2 Protein Kinase; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056744:Cyclin B1 / Q000235:genetics*; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D013454:Sulfoxides; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics*; D000097642:GADD45 Proteins
D016588:Anticarcinogenic Agents; D000943:Antigens, Differentiation; D016203:CDC2 Protein Kinase; D056744:Cyclin B1; D018844:Cyclin-Dependent Kinases; D017879:Isothiocyanates; D013454:Sulfoxides; C534699:CCNB1 protein, human; C086470:GADD45B protein, human; D000097642:GADD45 Proteins; C528899:CDK1 protein, human; C016766:sulforaphane
G2/M arrest; cervical cancer cells; cyclin B1/CDC2; growth arrest and DNA damage 45 (GADD45); sulforaphane