Growth hormone-releasing hormone antagonist induces apoptosis of human endometrial cancer cells through PKCδ-mediated activation of p53/p21

Cancer Letters
Hsien-Ming WuPeter C K Leung

Abstract

The growth hormone-releasing hormone (GHRH) antagonists have been shown to inhibit growth of human cancer cells, but the underlying molecular mechanisms and their actions have not been fully investigated. In this study, we first showed that GHRH-R splice variant 1 (SV1) was expressed in two human endometrial cancer cell lines, Ishikawa and ECC-1. By using MTT assay, immunoblotting for cleaved caspase-3 and TUNEL assays, we found that cell growth inhibition and apoptosis were induced in GHRH antagonist, JMR-132-treated cells by activating PKCδ and could be inhibited by treatment with PKC inhibitor, GF109203X. In addition, activation and protein expression of p53 as well as the expression of its downstream effector, p21, were increased by JMR-132 treatment. Moreover, JMR-132-induced p53 and p21 expression were diminished by treatment with PKC inhibitor. Knockdown of endogenous p53 and p21 by siRNAs abolished the JMR-132-induced cell growth inhibition and apoptosis. This study demonstrates a novel mechanism in which GHRH antagonist-induced cell growth inhibition and apoptosis through PKCδ-mediated activation of p53/p21 in human endometrial cancer cells. These findings may suggest the feasibility of GHRH antagonists as a therapeuti...Continue Reading

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Citations

Aug 15, 2013·Journal of Applied Toxicology : JAT·Qingyu HuangHeqing Shen
Mar 7, 2014·The Journal of Biological Chemistry·Kamalika SahaRichard L Eckert
Dec 9, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jinfeng GanHao Zhang
Jan 20, 2019·Proceedings of the National Academy of Sciences of the United States of America·Tania VillanovaRiccarda Granata

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