Medroxyprogesterone acetate alone or synergistic with chemotherapy suppresses colony formation and DNA synthesis in C6 glioma in vitro.
We have studied the effects of medroxyprogesterone acetate (MPA) on C6 glioma growth in vitro in order to prove the hypothesis that it could arrest growth and induce drug sensitisation in a glial tumour as it does in breast cancer cells. Plating, thymidine-labelling index, ultra-structure, and soft agar colony growth were determined after incubation with MPA, and/or cisplatin, procarbazine and methotrexate (MTX). MPA (microg/ml) reduced the thymidine-labelling index by 41 and 73% at 48 and 96 h, respectively, and decreased colony growth by 61%. Soft agar colony inhibition by MPA was almost as potent as MTX (0.3 microg/ml), but the latter drug showed very high cytotoxicity. Electron microscopy revealed that in medroxyprogesterone treated cells myeloid bodies developed, but MTX treatment caused mainly necrosis. Medroxyprogesterone increased procarbazine and cisplatin-induced colony growth and S-phase inhibition, but reduced MTX-induced thymidine-labelling inhibition. In conclusion, progesterone may inhibit growth and sensitize to drugs.
Altinoz
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Histology and Embryology Department, Istanbul Medical School, 34390, Istanbul, Turkey. maltinoz@hotmail.com
Bilir
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Ozar
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Onar
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Sav
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D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002945:Cisplatin / Q000633:toxicity; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004357:Drug Synergism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008525:Medroxyprogesterone / Q000627:therapeutic use / Q000633:toxicity*; D008727:Methotrexate / Q000633:toxicity; D008854:Microscopy, Electron; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D011344:Procarbazine / Q000633:toxicity; D045167:Progesterone Congeners / Q000627:therapeutic use / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D019384:Nucleic Acid Synthesis Inhibitors; D045167:Progesterone Congeners; D011344:Procarbazine; D004247:DNA; D008525:Medroxyprogesterone; D002945:Cisplatin; D008727:Methotrexate