Sulforaphene suppresses growth of colon cancer-derived tumors via induction of glutathione depletion and microtubule depolymerization

Mol Nutr Food Res. 2016 May;60(5):1068-78. doi: 10.1002/mnfr.201501011. Epub 2016 Mar 24.

Abstract

Scope: Cruciferous vegetables harbor a number of isothiocyanates that have been recognized for their cancer-related properties. Out of these, sulforaphene (a naturally occurring derivative of sulforaphane) has received little attention in studies of colon cancer and its mechanism of action remains to be elucidated.

Methods and results: We observed that sulforaphene inhibited growth of human colon cancer cell lines HCT116, HT-29, KM12, SNU-1040, and DLD-1, while exhibiting negligible toxicity toward nonmalignant cells. Sulforaphene induced G2/M phase cell cycle arrest and apoptosis of colon cancer cells analyzed by flow cytometry, concomitant with phosphorylation of CDK1 and CDC25B at inhibitory sites, and upregulation of the p38 and JNK pathways. It was further determined that sulforaphene is a potent inhibitor of microtubule polymerization while generating reactive oxygen species via the depletion of glutathione. These observations further extended into inhibitory effects against colon tumor growth in a mouse xenograft model.

Conclusion: These findings demonstrate that sulforaphene may contribute to the anti-tumor effects of cruciferous vegetables that contain sulforaphene and other isothiocyanates.

Keywords: Cancer; Glutathione; Microtubule depolymerization; Sulforaphene.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology*
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Glutathione / metabolism*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Isothiocyanates / pharmacology*
  • M Phase Cell Cycle Checkpoints / drug effects
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Nude
  • Microtubules / metabolism*
  • Reactive Oxygen Species / metabolism
  • Xenograft Model Antitumor Assays
  • cdc25 Phosphatases / genetics
  • cdc25 Phosphatases / metabolism
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Isothiocyanates
  • Reactive Oxygen Species
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • p38 Mitogen-Activated Protein Kinases
  • CDC25B protein, human
  • cdc25 Phosphatases
  • Glutathione
  • sulphoraphene