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Proliferative Properties of 17β‐aminoestrogens in MCF ‐7 Human Breast Cancer Cells
Author(s) -
Lemini Cristina,
Estela Avila María,
Medina Martha,
Sánchez Carlos,
Figueroa Alejandra,
GarcíaMondragón Maria Juana,
VargasVázquez Arsenio,
JiménezOrozco Alejandro
Publication year - 2017
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12674
Subject(s) - mcf 7 , human breast , breast cancer , cancer research , cancer , cancer cell , chemistry , biology , medicine
The 17β‐aminoestrogens ( AE s) prolame, butolame and pentolame are weakly oestrogenic in rodents and display anticoagulant properties in contrast to oestradiol (E 2 ) which presents pro‐coagulant effects, potentially thrombogenic. They possess anti‐anxiety and antidepressive properties, being good candidates for menopausal hormone therapy (MHT). Their capability to induce proliferation of MCF ‐7 human breast cancer cells, in which proliferative rate depends on oestrogens, has not been explored; thus, the aim of this work was to characterize it. AE s’ proliferation properties were evaluated compared with E 2 in MCF ‐7 carcinoma cell line cultures using established methods. Receptor mediation on cell proliferation was studied by co‐incubating them with the oestrogen receptor antagonists tamoxifen, ICI 182,780 and the selective antagonists MPP ( ER α) and PHTPP ( ER β). E 2 and AE s increased MCF ‐7 cell proliferation; their proliferative effect was between 1.5‐2 and E 2 = 3.6 compared with controls (0); their relative proliferative effect was 18–38% (E 2 = 100%) with a relative proliferative potency of 4.5–8.9 (E 2 = 100). The ER α antagonist MPP inhibited the MCF ‐7 cell proliferation induced by E 2 and AE s; on the contrary, the ER β antagonist PHTPP exacerbated the proliferative response, showing that the AE s’ proliferative activity was mainly ER α‐mediated and apparently controlled by ER β. Preliminary cytometric DNA flow analysis showed that AE s’ cell cycle S phase inducer property was lower than E 2 following the proliferative order: E 2 > butolame > prolame > pentolame, indicating pentolame with the weakest proliferative properties and being the safest of this series as a candidate for MHT .