SERPINA3K induces apoptosis in human colorectal cancer cells via activating the Fas/FasL/caspase-8 signaling pathway

Yachao Yao, Lei Li, Xuan Huang, Xiaoqiong Gu, Zumin Xu, Yang Zhang, Lijun Huang, Shuai Li, Zhiyu Dai, Cen Li, Ti Zhou, Weibin Cai, Zhonghan Yang, Guoquan Gao*, Xia Yang

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

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. SERPINA3K is a serine proteinase inhibitor with anti-angiogenic activities. However, it is unknown whether SERPINA3K has a direct impact on carcinoma cells. We reported for the first time that SERPINA3K-induced colorectal cancer cells apoptosis via the PPARγ/Fas/FasL signaling pathway. Therefore, our study provides additional insight into the direct anti-tumor function by inducing colorectal tumor cells apoptosis of SERPINA3K.

Original languageEnglish (US)
Pages (from-to)3244-3255
Number of pages12
JournalFEBS Journal
Volume280
Issue number14
DOIs
StatePublished - Jul 1 2013

Keywords

  • FasL
  • PPARγ
  • SERPINA3K
  • apoptosis
  • colorectal cancer

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yao, Y., Li, L., Huang, X., Gu, X., Xu, Z., Zhang, Y., Huang, L., Li, S., Dai, Z., Li, C., Zhou, T., Cai, W., Yang, Z., Gao, G., & Yang, X. (2013). SERPINA3K induces apoptosis in human colorectal cancer cells via activating the Fas/FasL/caspase-8 signaling pathway. FEBS Journal, 280(14), 3244-3255. https://doi.org/10.1111/febs.12303