Effects of different progestogens on human breast tumor cell growth

Abstract

Objective To examine the effect of progestogens currently used in hormone therapy on growth of human breast tumor cells.

Methods MCF-7 cells were incubated in 10 nmol/l progestogens, including progesterone (P4), medroxyprogesterone acetate (MPA), norethisterone acetate (NETA), and cyproterone acetate (CPA), with or without 17β-estradiol (E₂, 1 nmol/l and 10 nmol/l), as well as E₂ alone. Cell proliferation, apoptosis, and the expression of caspase-3 and proliferating cell nuclear antigen (PCNA) were evaluated.

Results The ratios of apoptosis : proliferation significantly increased in cultures with progestogens alone, 1 nmol/l E₂ plus progestogens (except P4), and 10 nmol/l E₂ plus NETA. Caspase-3 significantly diminished in cultures with E₂ alone; this was completely reversed when progestogens were added. MPA alone or with 1 nmol/l E₂ and 10 nmol/l E₂ plus NETA significantly increased caspase-3. Using progestogens alone, except P4, significantly decreased PCNA expression.

Conclusions The results demonstrate that various progestogens have different effects on growth of breast tumor cells, especially with the combined usage of E₂. Progestogen-induced apoptosis may be partly inhibited with the presence of E₂, but less severe with lower E₂ concentrations. Therefore, the choice of progestogens, as well as the doses of E₂ and/or progestogen, may influence breast cancer risk.

Key words:

• PROGESTOGEN
• 17β-ESTRADIOL
• HORMONE THERAPY
• APOPTOSIS
• CASPASE-3
• PROLIFERATING CELL NUCLEAR ANTIGEN

Conflict of interest  The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper.

Source of funding  Nil.