Abstract 1025: A prolyl-hydroxylase inhibitor, ethyl-3,4-dihydroxybenzoate, induces cell autophagy and apoptosis in esophageal squamous cell carcinoma cells

Abstract

Abstract The protocatechuic acid ethyl ester ethyl-3,4-dihydroxybenzoate (EDHB) is an antioxidant found in the testa of peanut seeds. The cytotoxic effect of EDHB on esophageal squamous cell carcinoma (ESCC) cells was investigated and 46 up- and down-regulated genes involved in several signaling pathways associated with cell cycle regulation and cellular metabolism were identified. Our studies have shown that EDHB can effectively induce autophagy and apoptosis of esophageal cancer cells by BNIP3 and NDRG1 respectively, and AKR1C family were one of the differentially expressed genes after cells treated with EDHB. We also found that the esophageal cancer cells with higher (KYSE 180) and lower (KYSE 510) AKR1C expressing levels were selected, and the cell proliferation was found inhibited more effectively in KYSE 180 than KYSE 510 cells after treated with EDHB. Furthermore, at the same condition, the effective subunits of AKR1C superfamily, AKR1C1/C2, were identified quantitatively by multiple reaction monitoring (MRM) assays. And the involvement of AKR1C1/C2 in the metabolism of the EDHB in ESCC cells and induced cell death. When autophagy was inhibited using 3-methyladenine (3-MA), KYSE 180 cells exhibited higher sensitivity to EDHB and it may act as metabolic substrate of AKR1C1/C2. These results indicate that esophageal cancer patients with high expression of AKR1C1/C2 are more sensitive to EDHB and facilitate its induced autophagy and apoptosis that providing potential guidance for the chemoprevention of ESCC. Citation Format: Wei Li, Guixue Hou, Dianrong Zhou, Xiaomin Lou, Yang Xu, Siqi Liu, Xiaohang Zhao. A prolyl-hydroxylase inhibitor, ethyl-3,4-dihydroxybenzoate, induces cell autophagy and apoptosis in esophageal squamous cell carcinoma cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1025.