Novel Melatonin, Estrogen, and Progesterone Hormone Therapy Demonstrates Anti-Cancer Actions in MCF-7 and MDA-MB-231 Breast Cancer Cells.

Autor: Hasan M; Division of Pharmaceutical, Administrative and Social Sciences, Graduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, PA, USA., Browne E; Division of Pharmaceutical, Administrative and Social Sciences, Graduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, PA, USA., Guarinoni L; Division of Pharmaceutical, Administrative and Social Sciences, Graduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, PA, USA., Darveau T; Division of Pharmaceutical, Administrative and Social Sciences, Graduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, PA, USA., Hilton K; Division of Pharmaceutical, Administrative and Social Sciences, Graduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, PA, USA., Witt-Enderby PA; Division of Pharmaceutical, Administrative and Social Sciences, Graduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, PA, USA.; UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Jazyk: angličtina
Zdroj: Breast cancer : basic and clinical research [Breast Cancer (Auckl)] 2020 Jun 24; Vol. 14, pp. 1178223420924634. Date of Electronic Publication: 2020 Jun 24 (Print Publication: 2020).
DOI: 10.1177/1178223420924634
Abstrakt: A novel melatonin, estrogen, and progesterone hormone therapy was developed as a safe bio-identical alternative hormone therapy for menopausal women based on the Women's Health Initiative findings that PremPro™ increased breast cancer risk and mortality of all types of breast cancer in postmenopausal women. For HER2 breast cancer, melatonin, estrogen, and progesterone delayed tumor onset and reduced tumor incidence in neu female mice. For other breast cancers, its actions are unknown. In this study, melatonin, estrogen, and progesterone hormone therapy were assessed in human ER+ (MCF-7) and triple negative breast cancer (MDA-MB-231) cells, and found to decrease proliferation and migration of both breast cancer lines. Inhibition of MEK1/2 and 5 using PD98059 and BIX02189, respectively, inhibited proliferation and migration in MDA-MB-231 cells and proliferation in MCF-7 cells; however, when combined with melatonin, estrogen, and progesterone, BIX02189 blocked melatonin, estrogen, and progesterone-mediated inhibition of migration in MCF-7 cells and induced Elf-5. For MDA-MB-231 cells, BIX02189 combined with melatonin, estrogen, and progesterone inhibited proliferation and increased pERK1/2 and β1-INTEGRIN; levels of pERK5 remained low/nearly absent in both breast cancer lines. These findings demonstrate novel anti-cancer actions of melatonin, estrogen, and progesterone in ER+ and triple negative breast cancer cells through intricate MEK1/2- and MEK5-associated signaling cascades that favor anti-proliferation and anti-migration.
Competing Interests: Declaration of Conflicting Interests:The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: P.A.W.-E., inventor, Duquesne University, assignee. Combination hormone replacement therapy (HRT) and melatonin to prevent and treat mammary cancer. US Patent 8618083 (2013) and 9370526 (2016). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(© The Author(s) 2020.)
Databáze: MEDLINE
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