Autophagy and nuclear changes in FM3A breast tumor cells after epirubicin, medroxyprogesterone and tamoxifen treatment in vitro.
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.
Bilir
A
A
Department of Histology and Embryology, Istanbul Medical Faculty, Istanbul, Turkey. bilira@istanbul.edu.tr
Altinoz
M A
MA
Erkan
M
M
Ozmen
V
V
Aydiner
A
A
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects* / Q000648:ultrastructure; D004357:Drug Synergism; D015251:Epirubicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008525:Medroxyprogesterone / Q000494:pharmacology*; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D013629:Tamoxifen; D015251:Epirubicin; D008525:Medroxyprogesterone