Premium
Medroxyprogesterone and tamoxifen augment anti‐proliferative efficacy and reduce mitochondria‐toxicity of epirubicin in FM3A tumor cells in vitro
Author(s) -
Altinoz Meric A.,
Bilir Ayhan,
Gedikoglu Gunduz,
Ozcan Emin,
Oktem Gulperi,
Muslumanoglu Mahmut
Publication year - 2007
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2006.11.013
Subject(s) - epirubicin , pharmacology , toxicity , clonogenic assay , anthracycline , mitochondrion , apoptosis , tamoxifen , chemistry , biology , medicine , breast cancer , biochemistry , cancer
We have shown that low doses of medroxyprogesterone acetate (MPA‐ 2.6 μM) and tamoxifen (TAM‐ 270 nM) could augment the effectiveness of epirubicin in breast tumor cells. In this study, we monitored early cell kinetics (24–96 h plating and S‐phase) and mitochondrial morphology during chemo‐endocrine treatments to delineate the epirubicin sensitizing mechanism. S‐phase fractions with radioactive thymidine uptake, plating efficacy, and transmission electron microscopic analysis were taken for 24‐h periods until the 7th day after drug treatments. Despite strongly enhancing the clonogenic killing, both MPA and TAM did not affect epirubicin induced early cytotoxicity. Instead, they augmented the S‐phase inhibition, which was even more pronounced for TAM. Epirubicin induced prominent swelling and crista damage of mitochondria and fragmentation of nuclei. Mitochondria were a normal size during a combination of epirubicin with either MPA‐ or tamoxifen treatment, despite the persistence of chromatin fragmentation and strong synergism on the clonogenic killing of breast tumor cells. Low dosage endocrine agent‐induced anthracycline sensitization may be independent of mitochondrial toxicity. Further studies would be worthwhile, since the uncoupling of mitochondrial toxicity from the anti‐neoplastic effect may also mean obviated cardiac toxicity in clinic.