Role of the Mitochondrial bc\-Complex in the Cytotoxic Action of Diethylstilbestrol-Diphosphate toward Prostatic Carcinoma Cells1

نویسندگان

  • Peter Schulz
  • Thomas A. Link
  • Laura Chaudhuri
  • Friedrich Fittier
چکیده

In previous work (P. Schulz et al., Cancer Res., 48: 2867-2870, 1988) we have demonstrated that diethylstilbestrol (DES), DES-monophosphatc, and DES-diphosphate (DESDP) are generally cytotoxic at con centrations attained in patients' sera during therapeutic DESDP infusions for progressed carcinoma of the prostate. \Ye have extended this work and addressed two questions: (a) Is DESDP itself a completely nontoxic prodrug which has to be transformed into the active species DES by a phosphatase? (/>) Which metabolic or regulatory mechanism in a cell is the target of DES action? Using cell cultures in phosphatase-depleted media we could provide evidence that DESDP exerts cytotoxic activity only after conversion to DES. Oxygen electrode experiments and differ ence spectra with intact mitochondria demonstrated that DES did not act as an uncoupler, but inhibited electron flow from ubiquinone to cytochrome <•,. Phenomena previously observed in DES-treated cells could be explained by distortion of the energy metabolism.

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تاریخ انتشار 2006