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Tunicamycin significantly reduces the MCF‐7 human breast cancer cell proliferation
Author(s) -
Trujillo Uldaeliz,
Banerjee Dipak K
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1009-d
Subject(s) - tunicamycin , apoptosis , cell cycle , cell growth , mcf 7 , cancer research , chemistry , programmed cell death , cancer cell , cancer , biology , microbiology and biotechnology , medicine , biochemistry , unfolded protein response , human breast
Breast cancer is the most frequently diagnosed cancer in women, accounting for one out of every eight women. The etiology of the disease is complex and requires neovascularization for the growth of a malignant tumor. Our laboratory has observed recently that tunicamycin, (a) an antibiotic, (b) a glucosamine‐containing pyrimidine nucleoside, and (c) a protein N‐glycosylation inhibitor reduces angiogenesis significantly. This was due to an induction of unfolded protein response‐mediated cell cycle arrest and apoptosis. The objective of our present study is to test the hypothesis that tunicamyin inhibits MCF‐7 cell proliferation. MCF‐7 cells ware synchronized by serum deprivation for 48 hours, and treated with tunicamycin (0–10 μg/ml) for 24 hours. The cell morphology was monitored by light microscopy. The cell growth was reduced only 20–30% at 0.1 μg/ml and 1.0 μg/ml of tunicamycin, respectively but the inhibition was >70% at 10 μg/ml of tunicamycin. There was no indication of the cell cycle arrest. Total Bcl‐2 expression was increased in the presence of 10 μg/ml and 0.1 μg/ml of tunicamycin as well as at “zero time”. Bak expression was not detected but a high level expression of Bax, Bad and p53 was detected at low tunicamycin concentration. There was no detectable expression of either caspase 3 or 9. Therefore, we conclude that tunicamycin‐mediated MCF‐7 cells death may not be due to an induction apoptosis. Flow cytometric evaluation of the cell cycle also supports such conclusion. Supported by NIH U54‐CA096297 and the Susan G. Komen Breast Cancer Foundation BCTR58206 grants.