Induction of apoptosis in MCF-7 and MDA-MB-231 breast cancer cells by Oligonol is mediated by Bcl-2 family regulation and MEK/ERK signaling.
Oligonol is a novel catechin-rich biotechnology product. The role of oligonol in modulating intracellular signaling mechanisms was investigated with the view of demonstrating its potential chemopreventive effect and the ability to inhibit cell proliferation using the estrogen-responsive MCF-7 and the estrogen-unresponsive MDA-MB-231 human breast cancer cell lines. Cell survival assay indicated that Oligonol was cytotoxic to both cells. Oligonol triggered apoptosis as revealed by the morphological features typical of nucleus staining and the accumulation of sub-G1 peak. Treatment with 25 microg/ml Oligonol resulted in an activation of caspase-7 and up-regulation of Bad on MCF-7 cells, while the Oligonol (20 microg/ml) induced up-regulation of Bcl-2 protein in a time-response manner on MDA-MB-231 cells. ERK1/2 in both cells were inactivated after Oligonol treatment in a time-dependent manner, and also inactivated upstream MEK1/2. Oligonol triggers apoptosis in MCF-7 and MDA-MB-231 cells through the modulation of pro-apoptotic Bcl-2 family proteins and MEK/ERK signaling pathway.
Jo
Eun-Hye
EH
Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Lee
Soo-Jin
SJ
Ahn
Nam-Shik
NS
Park
Joon-Suk
JS
Hwang
Jae-Woong
JW
Kim
Sung-Hoon
SH
Aruoma
Okezie I
OI
Lee
Yong-Soon
YS
Kang
Kyung-Sun
KS
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D053179:Caspase 7 / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000378:metabolism
D004273:DNA, Neoplasm; D010636:Phenols; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein; C514283:oligonol; D002392:Catechin; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D053179:Caspase 7