%0 Journal Article %T p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid %J Asian Pacific Journal of Cancer Prevention %I West Asia Organization for Cancer Prevention (WAOCP), APOCP's West Asia Chapter. %Z 1513-7368 %D 2014 %\ 11/01/2014 %V 15 %N 11 %P 4519-4525 %! p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid %K oleanolic acid %K Apoptosis %K p38 MAPK %K cancer %K ROS %R %X Oleanolic acid (OA) is a nutritional component widely distributed in various vegetables. Although it has beenwell recognized for decades that OA exerts certain anti-tumor activity by inducing mitochondria-dependentapoptosis, it is still unclear that what molecular signaling is responsible for this effect. In this study, we employedcancer cell lines, A549, BXPC-3, PANC-1 and U2OS to elucidate the molecular mechanisms underlying OA antitumoractivity. We found that activation of MAPK pathways, including p-38 MAPK, JNK and ERK, was triggeredby OA in both a dose and time-dependent fashion in all the tested cancer cells. Activation was accompaniedby cleavage of caspases and PARP as well as cytochrome C release. SB203580 (p38 MAPK inhibitor), but notSP600125 (JNK inhibitor) and U0126 (ERK inhibitor), rescued the pro-apoptotic effect of OA on A549 and BXPC-3 cells. OA induced p38 MAPK activation promoted mitochondrial translocation of Bax and Bim, and inhibitedBcl-2 function by enhancing their phosphorylation. OA can induce reactive oxygen species (ROS)-dependentASK1 activation, and this event was indispensable for p38 MAPK-dependent apoptosis in cancer cells. In vivo,p38 MAPK knockdown A549 tumors proved resistant to the growth-inhibitory effect of OA. Collectively, weelucidated that activation of ROS/ASK1/p38 MAPK pathways is responsible for the apoptosis stimulated byOA in cancer cells. Our finding can contribute to a better understanding of molecular mechanisms underlyingthe antitumor activity of nutritional components. %U https://journal.waocp.org/article_29273_1134d32a200447c15985ff9872cc2fbc.pdf