TY - JOUR
T1 - Niclosamide induced cell apoptosis via upregulation of ATF3 and activation of PERK in Hepatocellular carcinoma cells
AU - Weng, Shunyan
AU - Zhou, Liang
AU - Deng, Qing
AU - Wang, Jiaxian
AU - Yu, Yan
AU - Zhu, Jianwei
AU - Yuan, Yunsheng
N1 - Funding Information:
We would like to thank Weifeng Ma and Hao Xu from Shanghai Jiao Tong University(SJTU) help us to prepare some solutions and Evhy He from SJTU help us to review the manuscript. This work was supported by the National Natural and Science Foundation of China (Yunsheng Yuan, 81302825) and the Shanghai Key Laboratory of Veterinary Biotechnology (Yunsheng Yuan, klab201501).
Publisher Copyright:
© 2016 Weng et al.
PY - 2016/2/25
Y1 - 2016/2/25
N2 - Background: Hepatocellular carcinoma (HCC) is one of most common and aggressive human malignancies in the world, especially, in eastern Asia, and its mortality is very high at any phase. We want to investigate mechanism of niclosamide inducing cell apoptosis in HCC. Methods: Two hepatoma cell lines were used to evaluate activity of niclosamide inducing cell apoptosis and study its mechanism. Quantitative real-time PCR and western blotting were used in analysis of genes expression or protein active regulated by niclosamide. Results: Niclosamide remarkably induced cell apoptosis in hepatoma cells. Furthermore, our study revealed that RNA-dependent protein kinase-like kinase (PERK) is activated and its expression is up-regulated in HCC cells which are exposed to niclosamide. niclosamide also significantly increase activating transcription factor 3 (ATF3), activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein-homologous protein (CHOP) expression in HCC cells. It's suggested that the function of niclosamide was abrogated by PERK inhibitor or absent ATF3. Expression of PERK and CHOP is correlated with ATF3 level in the cells. Conclusion: Taken together, our results indicate that ATF3 plays an integral role in ER stress activated and cell apoptosis induced by niclosamide in HCC cells. In this study, the new mechanism of niclosamide as anti-cancer we investigated, too.
AB - Background: Hepatocellular carcinoma (HCC) is one of most common and aggressive human malignancies in the world, especially, in eastern Asia, and its mortality is very high at any phase. We want to investigate mechanism of niclosamide inducing cell apoptosis in HCC. Methods: Two hepatoma cell lines were used to evaluate activity of niclosamide inducing cell apoptosis and study its mechanism. Quantitative real-time PCR and western blotting were used in analysis of genes expression or protein active regulated by niclosamide. Results: Niclosamide remarkably induced cell apoptosis in hepatoma cells. Furthermore, our study revealed that RNA-dependent protein kinase-like kinase (PERK) is activated and its expression is up-regulated in HCC cells which are exposed to niclosamide. niclosamide also significantly increase activating transcription factor 3 (ATF3), activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein-homologous protein (CHOP) expression in HCC cells. It's suggested that the function of niclosamide was abrogated by PERK inhibitor or absent ATF3. Expression of PERK and CHOP is correlated with ATF3 level in the cells. Conclusion: Taken together, our results indicate that ATF3 plays an integral role in ER stress activated and cell apoptosis induced by niclosamide in HCC cells. In this study, the new mechanism of niclosamide as anti-cancer we investigated, too.
KW - Activating transcription factor 3
KW - Endoplasmic reticulum stress
KW - Liver cancer
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=84959100148&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959100148&partnerID=8YFLogxK
U2 - 10.1186/s12876-016-0442-3
DO - 10.1186/s12876-016-0442-3
M3 - Article
C2 - 26917416
AN - SCOPUS:84959100148
SN - 1471-230X
VL - 16
JO - BMC Gastroenterology
JF - BMC Gastroenterology
IS - 1
M1 - 25
ER -