EUROPEAN JOURNAL OF
PHARMACEUTICAL AND MEDICAL RESEARCH

( An ISO 9001:2015 Certified International Journal )

An International Peer Reviewed Journal for Pharmaceutical, Medical & Biological Sciences

An Official Publication of Society for Advance Healthcare Research (Reg. No. : 01/01/01/31674/16)

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 ISSN 2394-3211

Impact Factor: 7.065

 ICV - 79.57

Abstract

NON-PHENOLIC GESTODENE METABOLITES ENZYMATICALLY FORMED IN MCF-7 BREAST CANCER CELLS EFFICIENTLY INDUCE THE CELL PROLIFERATION

González Leticiaa, Santillán René, Damián-Matsumura Pablo, Lemus Ana Elenaa,*, (In Memory) Dr. Gregorio Pérez-Palacios

ABSTRACT

Gestodene, a synthetic 19-norprogestin has been used as contraceptive agent for millions of women. Epidemiological studies have raised concern over the relationship between contraceptive therapy with 19-norprogestins and a risk to develop breast cancer. Results from several studies have demonstrated that gestodene stimulates proliferation of estrogen-dependent MCF-7 breast cancer cells, effect that was inhibited by the presence of an antiestrogen, but not by an antiprogestin. A question arises because gestodene does not interact with estrogen receptors nor is able to be aromatized. Previous reports from our laboratory have shown that radiolabelled 19-norprogestins norethisterone and levonorgestrel, incubated with steroid target organs, undergo extensive enzymatic reductions on A-ring of their molecule, to form dihydro and tetrahydro metabolites which bind to estrogen receptor and were able to induce estrogen-like effects, in experimental models. The aim of the present study was to investigate the capacity of MCF-7 cells to metabolize [14C]-Gestodene, using an isotope dilution technique, as well as to determine the effect of gestodene and its reduced derivatives, to induce MCF-7 cell proliferation, in the presence or absence of steroid antagonists. Cell proliferation was determined by fluorometric quantitation of cell DNA content. Our results demonstrated that MCF-7 cells were able to biotransform gestodene into 5α-dihydro, 3α,5α-tetrahydro and 3β,5α-tetrahydro metabolites, which efficiently induced MCF-7 cell proliferation that was inhibited by the presence of an antiestrogen ICI 182,780, but neither by an antiprogestin RU 486 nor antiandrogen Flutamide. Our findings can contribute to understand the mode of action of gestodene to induce estrogen-like effects, such as MCF-7 cell proliferation.

Keywords: Gestodene, Breast cancer risk, Gestodene metabolism, Non-phenolic gestodene metabolites, MCF-7 cell proliferation.


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Google Scholar Indian Science Publications InfoBase Index (In Process) SOCOLAR, China Research Bible, Fuchu, Tokyo. JAPAN International Society for Research activity (ISRA) Scientific Indexing Services (SIS) Polish Scholarly Bibliography Global Impact Factor (GIF) (Under Process) Universal Impact Factor International Scientific Indexing (ISI), UAE Index Copernicus CAS (A Division of American Chemical Society) USA (Under Process) Directory of Open Access Journal (DOAJ, Sweden, in process) UDLedge Science Citation Index CiteFactor Directory Of Research Journal Indexing (DRJI) Indian citation Index (ICI) Journal Index (JI, Under Process) Directory of abstract indexing for Journals (DAIJ) Open Access Journals (Under Process) Impact Factor Services For International Journals (IFSIJ) Cosmos Impact Factor Jour Informatics (Under Process) Eurasian Scientific Journal Index (ESJI) International Innovative Journal Impact Factor (IIJIF) Science Library Index, Dubai, United Arab Emirates Pubmed Database [NLM ID: 101669306] (Under Process) IP Indexing (IP Value 2.40) Web of Science Group (Under Process) Directory of Research Journals Indexing Scholar Article Journal Index (SAJI) International Scientific Indexing ( ISI ) Scope Database Academia