Abstract 409: Docetaxel induced-JNK2/PHD1 signaling pathway increases cell death in cancer cells under hypoxia through the degradation of HIF-1{alpha}

In this study, we investigated the molecular mechanism underlying the docetaxel-induced degradation of HIF-1α and cell death in cancer cell under hypoxia. Pretreatment of docetaxel increased the polyubiquitination and proteasome mediated-degradation of HIF-1α and cell death in cancer cells under hypoxia. Under hypoxia, pharmacological inhibitors or siRNAs for PHD1 (prolyl hydroxylase 1) effectively prevented HIF-1α degradation and cancer cell death through inhibiting docetaxel-mediated activation of PHD1. In addition, siRNA-mediated knockdown of JNK2 blocked docetaxel-induced degradation of HIF-1α and cancer cell death through inhibiting the activation of PHD1. Through a luciferase reporter assay, we observed that the inhibition of the JNK2/PHD1 signaling pathway significantly suppressed the transcriptional activity of HIF-1α. Our results collectively show that, under hypoxia, docetaxel contributes to cause apoptotic cell death under hypoxia by triggering the JNK2/PHD1 signaling pathway, thereby increasing the degradation of HIF-1α.Citation Format: Eun-Taex Oh, Min-Jeong Song, Hyemi Lee, Yun-Jeong Choi, Heon Joo Park. Docetaxel induced-JNK2/PHD1 signaling pathway increases cell death in cancer cells under hypoxia through the degradation of HIF-1α. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 409. doi:10.1158/153...

Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Oh, E.-T., Song, M.-J., Lee, H., Choi, Y.-J., Park, H. J. Tags: Tumor Biology Source Type: research