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J Pharm Pharmacol ; 59(11): 1549-53, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17976267

RESUMEN

A new approach to the treatment of cancer is suggested, based on the innate overproduction of hydrogen peroxide in cancer cells. Hydrogen peroxide serves as a prodrug in the presence of transition metal ions, such as iron delivered by ferrocene. Under the effect of ferrocene, hydrogen peroxide is split into hydroxyl anions and highly reactive hydroxyl radicals. The latter cause oxidative DNA damage, which induces apoptosis, leading to elimination of cancer cells. Tamoxifen, a drug that interacts with oestrogen receptors, was used as a carrier to deliver ferrocene to breast cancer cells. For this aim tamoxifen conjugated to ferrocene (Tam-Fer) was synthesized. We have shown that the frequency of apoptotic events in MCF-7 breast cancer cells treated with Tam-Fer is significantly higher than in cells treated with tamoxifen or ferrocene separately. The increase of apoptosis correlates well with the rise in generation of reactive oxygen species in cancer cells. These results show that the hydrogen peroxide overproduced in tumour cells can serve as a prodrug for the treatment of cancer.


Asunto(s)
Antineoplásicos Hormonales/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Compuestos Ferrosos/farmacología , Peróxido de Hidrógeno/metabolismo , Tamoxifeno/farmacología , Antineoplásicos Hormonales/química , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/metabolismo , Daño del ADN/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Femenino , Compuestos Ferrosos/química , Humanos , Radical Hidroxilo/metabolismo , Metalocenos , Profármacos , Especies Reactivas de Oxígeno/metabolismo , Receptores de Estrógenos/metabolismo , Tamoxifeno/química , Células Tumorales Cultivadas
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