Key result
Epirubicin combined with medroxyprogesterone acetate or tamoxifen enhanced signs of autophagy, apoptotic blebs, chromatin fragmentation, and peculiar nuclear structures in FM3A breast tumor cells.
Why the study?
Does epirubicin combined with hormonal agents (MPA or tamoxifen) enhance autophagy and cell death in FM3A murine breast tumor cells?
Does epirubicin combined with hormonal agents (MPA or tamoxifen) enhance autophagy and cell death in FM3A murine breast tumor cells?
Hormonal agents such as MPA and tamoxifen can modulate the activity of anthracyclines like epirubicin, enhancing specific patterns of cell death and autophagy in breast tumor cells in vitro.
Hypothesis-generating for epirubicin-hormonal combinations in breast tumor models; leaves open any clinical translation.
OBJECTIVE: Autophagy is a form of physiological programmed cell death which is observable after hormonal withdrawal. In this study, the FM3A murine breast tumor cell line was treated with epirubicin alone and with medroxyprogesterone acetate (MPA) or tamoxifen, to determine if structural and kinetic signs of autophagy may also occur in an enhanced manner during epirubicin sensitization via hormonal agents. METHODS: One-week soft agar colony growth, 96-hour values of plating and pulse thymidine labeling and electron microscopical examinations were performed following treatment with MPA and tamoxifen alone or with epirubicin. RESULTS: Tamoxifen induced signs of autophagy, which was enhanced when it was combined with MPA. Epirubicin also induced autophagy of secretory granules, which coalesced to form an intracytoplasmic lumen. Combining MPA with epirubicin enhanced the formation of apoptotic blebs and chromatin fragmentation. When epirubicin was combined with tamoxifen, peculiar nuclear structures were formed. CONCLUSIONS: Hormonal agents may modulate anthracycline activity towards specific patterns in eliciting cell death, via autophagy and/or as yet unknown nucleolus-specific interactions.
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Bılır et al. (2001) studied Breast tumor (in vitro). Epirubicin alone and with medroxyprogesterone acetate (MPA) or tamoxifen vs. MPA and tamoxifen alone was evaluated on Structural and kinetic signs of autophagy and cell death. Epirubicin combined with medroxyprogesterone acetate or tamoxifen enhanced signs of autophagy, apoptotic blebs, chromatin fragmentation, and peculiar nuclear structures in FM3A breast tumor cells.
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