Chicoric Acid Induces Apoptosis in 3T3-L1 Preadipocytes through ROS-Mediated PI3K/Akt and MAPK Signaling Pathways

Abstract

Chicoric acid has been reported to possess various bioactivities. However, the antiobesity effects of chicoric acid remain poorly understood. In this study, we investigated the effects of chicoric acid on 3T3-L1 preadipocytes and its molecular mechanisms of apoptosis. Chicoric acid inhibited cell viability and induced apoptosis in 3T3-L1 preadipocytes which was characterized by chromatin condensation and poly ADP-ribose-polymerase (PARP) cleavage. Mitochondrial membrane potential (MMP) loss, Bax/Bcl-2 dysregulation, cytochrome c release, and caspase-3 activation were observed, indicating mitochondria-dependent apoptosis induced by chicoric acid. Furthermore, PI3K/Akt and MAPK (p38 MAPK, JNK, and ERK1/2) signaling pathways were involved in chicoric acid-induced apoptosis. The employment of protein kinase inhibitors LY294002, SB203580, SP600125, and U0126 revealed that PI3K/Akt signaling pathway interplayed with MAPK signaling pathways. Moreover, chicoric acid induced reactive oxygen species (ROS) generation. Pretreatment with the antioxidant N-acetylcysteine (NAC) significantly blocked cell death and changes of Akt and MAPK signalings induced by chicoric acid. In addition, chicoric acid down regulated HO-1 and COX-2 via the PI3K/Akt pathway.

MAPK pathway mediates the anti‑oxidative effect of chicoric acid against cerebral ischemia‑reperfusion injury in�vivo

“…The results of the present study suggest that chicoric acid has a protective effect following cerebral I/R injury, ameliorating increases in ROS generation, inflammation and NO and COX-2 levels in rats. It has also been reported that chicoric acid induces the apoptosis of 3T3-L1 preadipocytes and mediates COX-2, ROS, PI3K/AKT and p38-MAPK signaling pathways (13). Kour and Bani (11) revealed that chicoric acid suppressed inflammation in chronically stressed mice.…”

“…Chicoric acid induces the apoptosis of 3T3-L1 preadipocytes and mediates ROS, MAPK pathway mediates the anti-oxidative effect of chicoric acid against cerebral ischemia-reperfusion injury in vivo phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT) and p38-mitogen-activated protein kinase (MAPK) signaling pathways (12,13). The aim of the present study was to investigate the protective effect of chicoric acid on oxidative stress and inflammation in rats with cerebral I/R injury.…”

An Undesired Effect of Chemotherapy

“…The PI3K/Akt and MAPK signaling pathways have been shown to be activated by ROS (16,19,21). In other studies, NF-B and HIF-1␣ are shown to be the downstream targets of PI3K/Akt and/or ERK (22)(23)(24).…”

Chicoric acid: chemistry, distribution, and production

“…Chicoric acid properties have been reported to include anti-cancer, anti-obesity, antiviral, and anti-diabetic (King and Robinson, 1998; Pluymers et al, 2000; Charvat et al, 2006; Queffelec et al, 2008; Tousch et al, 2008; Tsai et al, 2012; Azay-Milhau et al, 2013; Xiao et al, 2013). For example, chicoric acid and its analogs have been claimed to possess anti-Human Immunodeficiency Virus (HIV) activity due to its involvement in HIV integrase inhibition, which could perhaps hinder HIV strain replication (King and Robinson, 1998; Charvat et al, 2006; Queffelec et al, 2008).…”