Evaluation of cytotoxic properties of organometallic ferrocifens on melanocytes, primary and metastatic melanoma cell lines.
Malignant melanoma is one of the most severe forms of skin cancer, and chemotherapeutic agents currently in use are poorly effective in curing the disease. Here we describe the properties of two organometallic ferrocenyl derivatives, ferrocifen (Fc-OH-Tam) and ferrociphenol (Fc-diOH) that show a specific antiproliferative effect on melanoma cells. After a short incubation period, Fc-OH-Tam is highly cytotoxic on melanoma cells but less toxic on melanocytes. Fc-diOH is slightly toxic at a high concentration but no discrepancy is observed between malignant and normal cells. After a long incubation time the latter is highly toxic for malignant cells but not for normal cells while the former was very highly toxic for primary malignant cells and significantly less toxic for normal cells. We also found that oxidative stress is not implicated in the mechanism of cytotoxicity, since both derivatives neither induce reactive oxygen species (ROS) level in melanocytes nor in melanoma cells. Finally, investigation on hair follicle growth revealed that the two organometallic derivatives induced an irreversible ejection of the hair shaft, thus predicting a potential hair loss side effect if used as a chemotherapeutic treatment.
Michard
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L'Oréal Recherche, 90 rue du Général Roguet, 92583 Clichy Cedex, France.
Jaouen
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G
Vessieres
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A
Bernard
B A
BA
D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004353:Drug Evaluation, Preclinical; D005296:Ferrous Compounds / Q000633:toxicity*; D018859:Hair Follicle / Q000187:drug effects; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D009362:Neoplasm Metastasis / Q000473:pathology; D009942:Organometallic Compounds / Q000633:toxicity; D018384:Oxidative Stress
D000970:Antineoplastic Agents; D005296:Ferrous Compounds; D009942:Organometallic Compounds; C514120:ferrocifen; C533771:ferrociphenol