Laura Muñoz-Moreno1, Andrew V Schally2,3, Juan C Prieto1, M José Carmena1, Ana M Bajo1. 1. Department of Systems Biology, University of Alcalá, Alcalá de Henares, Madrid, Spain. 2. Veterans Affairs Medical Center, Miami, Florida. 3. Departments of Pathology and Medicine, Divisions of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, Florida.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: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. CONCLUSIONS: 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.
Authors: Yuanhao Chang; Ruoyu Huang; You Zhai; Lijie Huang; Yuemei Feng; Di Wang; Ruichao Chai; Wei Zhang; Huimin Hu Journal: Ann Transl Med Date: 2021-03
Authors: Xiao Xiong; Xiurong Ke; Lu Wang; Zhimeng Yao; Yi Guo; Xianyang Zhang; Yuping Chen; Chi Pui Pang; Andrew V Schally; Hao Zhang Journal: Proc Natl Acad Sci U S A Date: 2020-03-10 Impact factor: 11.205