Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines.

Abstract

Sulforaphane, an isothiocyanate found in cruciferous vegetables, has been shown to induce phase 2 detoxication enzymes and inhibit the growth of chemically induced mammary tumors in rats, although the exact mechanisms of action of sulforaphane are not understood. In this study, we evaluated the effects of sulforaphane on cell growth and death in several human breast cancer cell lines and examined the hypothesis that sulforaphane acts as a histone deacetylase (HDAC) inhibitor in these cell lines. Sulforaphane treatment inhibited cell growth, induced a G(2)-M cell cycle block, increased expression of cyclin B1, and induced oligonucleosomal DNA fragmentation in the four human breast cancer cell lines examined, MDA-MB-231, MDA-MB-468, MCF-7, and T47D cells. Activation of apoptosis by sulforaphane in MDA-MB-231 cells seemed to be initiated through induction of Fas ligand, which resulted in activation of caspase-8, caspase-3, and poly(ADP-ribose) polymerase, whereas apoptosis in the other breast cancer cell lines was initiated by decreased Bcl-2 expression, release of cytochrome c into the cytosol, activation of caspase-9 and caspase-3, but not caspase-8, and poly(ADP-ribose) polymerase cleavage. Sulforaphane inhibited HDAC activity and decreased the expression of estrogen receptor-alpha, epidermal growth factor receptor, and human epidermal growth factor receptor-2 in each cell line, although no change in the acetylation of H3 or H4 was seen. These data suggest that sulforaphane inhibits cell growth, activates apoptosis, inhibits HDAC activity, and decreases the expression of key proteins involved in breast cancer proliferation in human breast cancer cells. These results support testing sulforaphane in vivo and warrant future studies examining the clinical potential of sulforaphane in human breast cancer.

• Authors: Allison Pledgie-Tracy, Michele D Sobolewski, Nancy E Davidson
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 6 Issue 3 Pg. 1013-21 (Mar 2007) ISSN: 1535-7163 [Print] United States
• PMID: 17339367 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Antineoplastic Agents
• CCNB1 protein, human
• Ccnb1 protein, rat
• Cyclin B
• Cyclin B1
• Estrogen Receptor alpha
• Fas Ligand Protein
• Isothiocyanates
• Proto-Oncogene Proteins c-bcl-2
• Sulfoxides
• Thiocyanates
• Cytochromes c
• ErbB Receptors
• Caspases
• sulforaphane

Topics

• Anticarcinogenic Agents (pharmacology)
• Antineoplastic Agents
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Caspases (metabolism)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Cyclin B (metabolism)
• Cyclin B1
• Cytochromes c (metabolism)
• Cytosol (metabolism)
• ErbB Receptors (metabolism)
• Estrogen Receptor alpha (metabolism)
• Fas Ligand Protein (metabolism)
• Humans
• Isothiocyanates
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Signal Transduction (drug effects)
• Sulfoxides
• Thiocyanates (pharmacology)
• Tumor Cells, Cultured