Alpha-eleostearic acid suppresses proliferation of MCF-7 breast cancer cells via activation of PPARgamma and inhibition of ERK 1 / 2.
Alpha-eleostearic acid (alpha-ESA) is known to suppress the growth in cancer cells although its underlying molecular mechanisms have not been fully elucidated. The present study was designed to elucidate and evaluate the anticancer mechanism of alpha-ESA on MCF-7 breast cancer cells. Also, an attempt was made to better understand the anticancer mechanism by which alpha-ESA activated PPARgamma and attenuated the ERK1/2 MAPK phosphorylation state. The MCF-7 breast cancer cell-line and nontumorigenic MCF-10A human mammary epithelial cells were treated with alpha-ESA and compared with negative control (without treatment) and positive control groups (treated with rosiglitazone), and changes of apoptosis-related molecules, PPARgamma and pERK1/2 were examined. In MCF-7 cells treated with alpha-ESA, we found that the expression of p53, p21, and Bax was up-regulated whereas expression of Bcl-2 and procaspase-9 was down-regulated. Moreover, nuclear translocation of PPARgamma by alpha-ESA positively correlated with inhibition of ERK1/2 activation. Our data suggest that alpha-ESA can be considered to be a PPARgamma agonist and thus a candidate for a chemotherapeutic agent against breast cancer.
Moon
Hyun-Seuk
HS
Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea.
Guo
Ding-Ding
DD
Lee
Hong-Gu
HG
Choi
Yun-Jaie
YJ
Kang
Jae-Seong
JS
Jo
Kyungmin
K
Eom
Jung-Min
JM
Yun
Cheol-Heui
CH
Cho
Chong-Su
CS
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000032:analysis; D005260:Female; D006801:Humans; D008042:Linolenic Acids / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors*; D047495:PPAR gamma / Q000032:analysis / Q000502:physiology*; D010766:Phosphorylation
D047628:Estrogen Receptor alpha; D008042:Linolenic Acids; D047495:PPAR gamma; C004934:eleostearic acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3