Alpha‐eleostearic acid suppresses proliferation of MCF‐7 breast cancer cells via activation of PPARγ and inhibition of ERK 1 / 2

Abstract

Alpha-eleostearic acid (a-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 a-ESA on MCF-7 breast cancer cells. Also, an attempt was made to better understand the anticancer mechanism by which a-ESA activated PPARc 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 a-ESA and compared with negative control (without treatment) and positive control groups (treated with rosiglitazone), and changes of apoptosisrelated molecules, PPARc and pERK1 ⁄ 2 were examined. In MCF-7 cells treated with a-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 PPARc by a-ESA positively correlated with inhibition of ERK1 ⁄ 2 activation. Our data suggest that a-ESA can be considered to be a PPARc agonist and thus a candidate for a chemotherapeutic agent against breast cancer. (Cancer Sci 2010; 101: 396-402)

Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells

“…The total amount of unsaturated fatty acids was almost three times more than that of saturated fatty acids, and, in particular, MUFAs account for about 68% of total fatty acids. There is increasing evidence that unsaturated free fatty acids can cause cell death by promoting apoptosis in breast cancer cells (Bocca et al, 2010;Grossmann et al, 2009;Moon et al, 2010;Yuan et al, 2009). PUFAs have been reported to be the most effective (Hawkins et al, 1999), but an increasing attention has been given the role of MUFAs in the last few years (Escrich et al, 2007).…”

Phosphorylation of Extracellular Signal-Regulated Kinase (ERK)-1/2 Is Associated with the Downregulation of Peroxisome Proliferator-Activated Receptor (PPAR)-γ during Polymicrobial Sepsis

“…Additionally, phosphorylation of PPARγ promotes its degradation through the ubiquitin-proteasome system (10). In MCF-7 breast cancer cells, inhibition of p-ERK1/2 with α-eleostearic acid correlated with decreased PPARγ in a timedependent manner (21). An alternative mechanism resulting in decreased nuclear PPARγ expression and activity could occur through direct interaction of nuclear PPARγ with MEKs, resulting in the nuclear export of PPARγ, thereby preventing its nuclear activation (22).…”

Growth inhibition and apoptotic effect of alpha-eleostearic acid on human breast cancer cells

“…It induced apoptosis and autophagy of human cervical cancer cells (HeLa) through reactive oxygen species (ROS) generation [38], but the underlying molecular mechanisms of a-ESA's action on cancer cells have not been fully elucidated [39].…”