Cycle arrest and apoptosis in MDA-MB-231/Her2 cells induced by curcumin.
Breast cancers with an overexpression of Her-2 or Skp2 overlap with those affected by reduced p27 expression. In breast cancer, the loss of p27 is associated with a poor prognosis. Curcumin, the main constituent of turmeric, has been found to stabilize p27 levels in breast cancer, but whether this effect is mediated through changes in Skp2 or Her2 expression remains unclear. This study investigates whether curcumin inhibits Skp2-mediated p27 ubiquitination in Her2/Skp2-overexpressing cancer cell lines (MDA-MB-231/Her2 cells). The results show that curcumin represses cell proliferation, induces G1 arrest at a lower dosage (30μM), triggers apoptosis at a higher dosage (50μM) and blocks cell migration in MDA-MB-231/Her2 cells. A low dose of curcumin increases p27 and decreases Skp2, Her2, Cyclin E, CDK kinases in a time- and dose-dependent manner, suggesting that p27, Skp2 and Her2 may be involved in the growth inhibition in MDA-MB-231/Her2 cells induced by curcumin. However, higher doses of curcumin produce a dose-dependent apoptotic death in MDA-MB-231/Her2 cells, which is related to cleaved forms of PARP and caspase 3. The findings indicate that curcumin is of potential value for the chemoprevention of breast cancer, especially in breast cancer with Skp2/Her2 overexpression.
Institutes of Biochemistry and Molecular Biology, College of Medicine National Taiwan University, Taipei, Taiwan.
Shih-Han
SH
Sun
Hsiu-Chen
HC
Huang
Cheng
C
Huang
Jen-Kun
JK
Lin
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009362:Neoplasm Metastasis; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D054875:Ubiquitination / Q000187:drug effects
D000970:Antineoplastic Agents; D003474:Curcumin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D044786:S-Phase Kinase-Associated Proteins; C508053:ERBB2 protein, human