Efficacy of sulforaphane is mediated by p38 MAP kinase and caspase-7 activations in ER-positive and COX-2-expressed human breast cancer cells.
Sulforaphane is an antioxidant and a potent stimulator of natural detoxifying enzyme and associated with lowered risk of cancer that is associated with the consumption of cruciferous vegetables. The chemopreventive effects of SFN was investigated using the MCF-7 human breast cancer cells and the M13SV1-immortalized human breast luminal epithelial cells. Sulforaphane reduced proliferation in MCF-7 cells and inhibited cyclooxygenase-2 expression in M13SV1 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). The chemopreventive effects of sulforaphane were associated with p38 mitogen-activated protein kinase suggest its important role in cell survival/apoptosis regulation and stabilization of cyclooxygenase-2. Sulforaphane upregulates p38 in MCF-7 cells and prevented TPA-reduced phosphorylation of p38 in M13SV1 cells, but activated caspase-7 associated with apoptosis in MCF-7 cells. These results suggest that sulforaphane may be an alternative candidate for targeted prevention of ER-positive and cyclooxygenase-2-induced phenotypes and breast cancer.
Jo
Eun-Hye
EH
Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine Kwanak-gu, Korea.
Kim
Sung-Hoon
SH
Ahn
Nam-Shik
NS
Park
Joon-Suk
JS
Hwang
Jae-Woong
JW
Lee
Yong-Soon
YS
Kang
Kyung-Sun
KS
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D053179:Caspase 7 / Q000378:metabolism*; D002461:Cell Line, Transformed; D053144:Cell Nucleus Shape / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics*; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017879:Isothiocyanates; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics*; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000970:Antineoplastic Agents; D017879:Isothiocyanates; D011960:Receptors, Estrogen; D013454:Sulfoxides; D013861:Thiocyanates; D051546:Cyclooxygenase 2; D011065:Poly(ADP-ribose) Polymerases; D048051:p38 Mitogen-Activated Protein Kinases; D053179:Caspase 7; C016766:sulforaphane