Growth hormone-releasing hormone receptor antagonists modify molecular machinery in the progression of prostate cancer

The Prostate
Laura Muñoz-MorenoAna M Bajo

Abstract

Therapeutic strategies should be designed to transform aggressive prostate cancer phenotypes to a chronic situation. To evaluate the effects of the new growth hormone-releasing hormone receptor (GHRH-R) antagonists: MIA-602, MIA-606, and MIA-690 on processes associated with cancer progression as cell proliferation, adhesion, migration, and angiogenesis. We used three human prostate cell lines (RWPE-1, LNCaP, and PC3). We analyzed several molecules such as E-cadherin, β-catenin, Bcl2, Bax, p53, MMP2, MMP9, PCNA, and VEGF and signaling mechanisms that are involved on effects exerted by GHRH-R antagonists. GHRH-R antagonists decreased cell viability and provoked a reduction in proliferation in LNCaP and PC3 cells. Moreover, GHRH-R antagonists caused a time-dependent increase of cell adhesion in all three cell lines and retarded the wound closure with the highest value with MIA-690 in PC3 cells. GHRH-R antagonists also provoked a large number of cells in SubG0 phase revealing an increase in apoptotic cells in PC3 cell line. Taken all together, GHRH-R antagonists of the MIAMI series appear to be inhibitors of tumor progression in prostate cancer and should be considered for use in future therapeutic strategies on this malignancy.

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Citations

Jan 20, 2019·Proceedings of the National Academy of Sciences of the United States of America·Tania VillanovaRiccarda Granata
Oct 24, 2019·Cancers·Mirela Diana IliePhilippe Bertolino
Mar 12, 2020·Proceedings of the National Academy of Sciences of the United States of America·Xiao XiongHao Zhang

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