title: SERPINA3K induces apoptosis in human colorectal cancer cells via activating the Fas/FasL/caspase-8 signaling pathway.
abstract: SERPINA3K, also known as kallikrein-binding protein (KBP), is a serine proteinase inhibitor with anti-inflammatory and anti-angiogenic activities. Our previous studies showed that SERPINA3K inhibited proliferation in a dose-dependent manner and induced apoptosis of endothelial cells but had no influence on SGC-7901 gastric carcinoma cells or HepG2 hepatocarcinoma cells. However, it is unknown whether SERPINA3K has a direct impact on other carcinoma cells and which mechanisms are involved. In this study, we report for the first time that SERPINA3K not only decreased cell viability but also induced apoptosis in the colorectal carcinoma cell lines SW480 and HT-29. SERPINA3K-induced apoptosis of SW480 and HT-29 was rescued by interference with Fas ligand (FasL) small hairpin RNA. Moreover, SERPINA3K increased the expression of FasL and activated caspase-8. Peroxisome proliferator-activated receptor γ (PPARγ), a transcription factor of FasL, was also upregulated by SERPINA3K in a dose-dependent manner. The upregulation effect of FasL induced by SERPINA3K was reversed after interference with PPARγ small interfering RNA. These results demonstrated that SERPINA3K-induced SW480 and HT-29 cell apoptosis was mediated by the PPARγ/Fas/FasL signaling pathway. Therefore, our study provides additional insight into the direct anti-tumor function by inducing tumor cell apoptosis of SERPINA3K in colorectal tumors.
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yachao
authors.initials: Y
authors.lastname: Yao
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Xuan
authors.initials: X
authors.lastname: Huang
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Gu
authors.forename: Zumin
authors.initials: Z
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lijun
authors.initials: L
authors.lastname: Huang
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Dai
authors.forename: Cen
authors.initials: C
authors.lastname: Li
authors.forename: Ti
authors.initials: T
authors.lastname: Zhou
authors.forename: Weibin
authors.initials: W
authors.lastname: Cai
authors.forename: Zhonghan
authors.initials: Z
authors.lastname: Yang
authors.forename: Guoquan
authors.initials: G
authors.lastname: Gao
authors.forename: Xia
authors.initials: X
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D019073:HT29 Cells; D006801:Humans; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015843:Serpins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D047495:PPAR gamma; D034741:RNA, Small Interfering; D015843:Serpins; D019014:fas Receptor; C051324:kallistatin; C505530:CASP8 protein, human; D053181:Caspase 8
keywords: FasL; PPARγ; SERPINA3K; apoptosis; colorectal cancer