Effects of Curcumin on Tobacco Smoke-induced Hepatic MAPK Pathway Activation and Epithelial-Mesenchymal TransitionIn Vivo

Abstract

Tobacco smoke is a major risk factor for hepatic cancer. Epithelial-mesenchymal transition (EMT) induced by tobacco smoke is crucially involved in the initiation and development of cancer. Mitogen-activated protein kinase (MAPK) pathways play important roles in tobacco smoke-associated carcinogenesis including EMT process. The chemopreventive effect of curcumin supplementation against cancers has been reported. In this study, we investigated the effects of tobacco smoke on MAPK pathway activation and EMT alterations, and then the preventive effect of curcumin was examined in the liver of BALB/c mice. Our results indicated that exposure of mice to tobacco smoke for 12 weeks led to activation of ERK1/2, JNK, p38 and ERK5 pathways as well as activator protein-1 (AP-1) proteins in liver tissue. Exposure of mice to tobacco smoke reduced the hepatic mRNA and protein expression of the epithelial markers, while the hepatic mRNA and protein levels of the mesenchymal markers were increased. Treatment of curcumin effectively attenuated tobacco smoke-induced activation of ERK1/2 and JNK MAPK pathways, AP-1 proteins and EMT alterations in the mice liver. Our data suggested the protective effect of curcumin in tobacco smoke-triggered MAPK pathway activation and EMT in the liver of BALB/c mice, thus providing new insights into the chemoprevention of tobacco smoke-associated hepatic cancer. Copyright © 2017 John Wiley & Sons, Ltd.

Curcumin sensitized the antitumour effects of irradiation in promoting apoptosis of oesophageal squamous-cell carcinoma through NF-κB signalling pathway

“…proposed the proliferation‐inhibitory and apoptosis‐inducing effects of curcumin on papillary thyroid cancer cells was mediated by the ROS production and impairment of mitochondrial membrane potential. Whereas in hepatocarcinoma, Liang et al . demonstrated the effects of curcumin on tobacco smoke‐induced hepatic MAPK pathway activation and epithelial–mesenchymal transition in vivo , and Kim et al .…”

“…Song et al [36] proposed the proliferation-inhibitory and apoptosis-inducing effects of curcumin on papillary thyroid cancer cells was mediated by the ROS production and impairment of mitochondrial membrane potential. Whereas in hepatocarcinoma, Liang et al [37] demonstrated the effects of curcumin on tobacco smoke-induced hepatic MAPK pathway activation and epithelial-mesenchymal transition in vivo, Figure 3 Curcumin improve the survival rate in xenograft tumour models. Xenograft tumour model was generated by ESCC-07 cell lines treated with PBS, irradiation alone (20 Gy in three fractions every 4 days), curcumin alone (10 lM daily for 12 consecutive days) or irradiation combined with curcumin (irradiation was performed at day 4, 8 and 12 after injection of 10 lM curcumin which began at day 1 for 12 consecutive days).…”

Curcumin inhibits superoxide dismutase-induced epithelial-to-mesenchymal transition via the PI3K/Akt/NF-κB pathway in pancreatic cancer cells

“…More importantly, curcumin is associated with minimal toxicity and it is safe at a high dose, as demonstrated by human clinical trials, in contrast with conventional cytotoxic drugs (35). Curcumin exerts its anticancer effects via multiple signaling pathways, such as Notch, mammalian target of rapamycin (mTOR), MAPK and NF-κB (5,(36)(37)(38)(39). Zhou et al (36) proved that curcumin suppressed pancreatic cancer cell growth, induced apoptosis and cell cycle arrest, weakened clonogenic potential, and inhibited migration and invasion via suppression of YAP/TAZ and Notch signaling.…”

“…It possesses several biological properties, including anti-inflammatory and anti-oxidant properties, and also plays a key role in inhibiting the initiation, progression and metastasis of several tumors (4). Curcumin exerts its anticancer effects by targeting multiple intracellular signaling pathways, including mitogen-activated protein kinase (MAPK), nuclear factor (NF)-κB, Akt and Wnt/β-catenin, among others (5)(6)(7). In addition, we recently demonstrated that curcumin inhibited hypoxia-induced epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells via blockade of the hedgehog signaling pathway (8).…”

Turmeric (Curcuma longa) and its major constituent (curcumin) as nontoxic and safe substances: Review

“…Curcumin as anticancer agent (Allegra et al, ) has good effects in head and neck squamous cell carcinoma (Wilken, Veena, Wang, & Srivatsan, ), and also, it is effective in suppressing gastric, colon, and breast cancer (Banik, Parasuraman, Adhikary, & Othman, ; Khosropanah et al, ; Liu, Xiang, Wu, & Wang, ; Tong, Wang, Sun, & Suo, ). It has preventive effects on tobacco smoke‐induced liver cancer (Liang et al, ). Recently, this agent has shown antimetastatic effect (de Campos et al, ; Deng, Verron, & Rohanizadeh, ).…”