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Cited by 25Estrogen and related hormone effectsGrowth Hormone and Insulin-like Growth FactorsPharmacological Effects and Assays

Nandrolone and stanozolol upregulate aromatase expression and further increase IGF-I-dependent effects on MCF-7 breast cancer cell proliferation

Sirianni, Rosa, Capparelli, Claudia, Chimento, Adele, Panza, Salvatore, Catalano, Stefania, Lanzino, Marilena, Pezzi, Vincenzo, Andò, Sebastiano·2012·Molecular and Cellular Endocrinology
DOI 10.1016/j.mce.2012.08.002
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Abstract

Several doping agents, such as anabolic androgenic steroids (AAS) and peptide hormones like insulin-like growth factor-I (IGF-I), are employed without considering the potential deleterious effects that they can cause. In addition, androgens are used in postmenopausal women as replacement therapy. However, there are no clear guidelines regarding the optimal therapeutic doses of androgens or long-term safety data. In this study we aimed to determine if two commonly used AAS, nandrolone and stanozolol, alone or in combination with IGF-I, could activate signaling involved in breast cancer cell proliferation. Using a human breast cancer cell line, MCF-7, as an experimental model we found that both nandrolone and stanozolol caused a dose-dependent induction of aromatase expression and, consequently, estradiol production. Moreover, when nandrolone and stanozolol were combined with IGF-I, higher induction in aromatase expression was observed. This increase involved phosphatidylinositol 3-kinase (PI3K)/AKT and phospholipase C (PLC)/protein kinase C (PKC), which are part of IGF-I transductional pathways. Specifically, both AAS were able to activate membrane rapid signaling involving IGF-I receptor, extracellular regulated protein kinases 1/2 (ERK1/2) and AKT, after binding to estrogen receptor (ER), as confirmed by the ability of the ER antagonist ICI182, 780 to block such activation. The estrogenic activity of nandrolone and stanozolol was further confirmed by their capacity to induce the expression of the ER-regulated gene, CCND1 encoding for the cell cycle regulator cyclin D1, which represents a key protein for the control of breast cancer cell proliferation. In fact, when nandrolone and stanozolol were combined with IGF-I, they increased cell proliferation to levels higher than those elicited by the single factors. Taken together these data clearly indicate that the use of high doses of AAS, as occurs in doping practice, may increase the risk of breast cancer. This potential risk is higher when AAS are used in association with IGF-I. To our knowledge this is the first report directly associating AAS with this type of cancer.

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  • Numerous studies have documented oncogenic properties of male steroid hormones and their derivatives on several human organs, including testis, liver, breast, and others.

    “Numerous studies have documented oncogenic properties of male steroid hormones and its derivatives on several human organs, including testis, liver, breast, and others (Sirianni et al., 2012; Salerno et al., 2018).”

    From An Arthropod Hormone, Ecdysterone, Inhibits the Growth of Breast Cancer Cells via Different Mechanisms (2020) · cites this paper as Sirianni et al., 2012

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Authors
Sirianni, R., Capparelli, C., Chimento, A., Panza, S., Catalano, S., Lanzino, M., Pezzi, V., & Andò, S.
Affiliations
University of Calabria (IT)
Corresponding author
Pezzi, Vincenzo
ORCID
Venue
Molecular and Cellular Endocrinology
Publisher
Elsevier BV
Published
2012-11
Volume
363
Issue
1-2
Pages
100-110
ISSN
0303-7207 (ISSN-L)
DOI
10.1016/j.mce.2012.08.002
OpenAlex
W2001955769
Cited by
25
References
64
Citations by year
2025: 1 · 2024: 1 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 1
FWCI
1.73
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Molecular and Cellular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
Funders
Ministero della Salute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Pharmacological Effects and Assays
Keywords
nandrolone, stanozolol, anabolic steroids, insulin-like growth factor I, aromatase expression, estradiol production, breast cancer cell proliferation, MCF-7 cells, PI3K/Akt signaling, IGF-1 receptor, ERK1/2, Akt, estrogen receptor, fulvestrant, cyclin D1, doping, cancer risk
MeSH terms
Androgens, Aromatase, Breast Neoplasms, Cell Survival, Drug Synergism, Enzyme Induction, Estradiol, Female, Humans, Insulin-Like Growth Factor I, Nandrolone, Type C Phospholipases, Stanozolol, Signal Transduction, Up-Regulation, Genes, Reporter, Phosphatidylinositol 3-Kinases, Anabolic Agents, Estrogen Receptor alpha, Cell Proliferation, Luciferases, Renilla, Proto-Oncogene Proteins c-akt, MCF-7 Cells

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