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

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.

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- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

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- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

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- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma.