Sulforaphane, a Dietary Isothiocyanate, Induces G₂/M Arrest in Cervical Cancer Cells through CyclinB1 Downregulation and GADD45β/CDC2 Association

Int J Mol Sci. 2016 Sep 12;17(9):1530. doi: 10.3390/ijms17091530.

Abstract

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.

Keywords: G2/M arrest; cervical cancer cells; cyclin B1/CDC2; growth arrest and DNA damage 45 (GADD45); sulforaphane.

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Antigens, Differentiation / genetics
  • CDC2 Protein Kinase
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin B1 / genetics*
  • Cyclin-Dependent Kinases / genetics*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Female
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • HeLa Cells
  • Humans
  • Isothiocyanates / pharmacology*
  • Sulfoxides
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / genetics*

Substances

  • Anticarcinogenic Agents
  • Antigens, Differentiation
  • CCNB1 protein, human
  • Cyclin B1
  • GADD45B protein, human
  • Isothiocyanates
  • Sulfoxides
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Cyclin-Dependent Kinases
  • sulforaphane