Targeted destruction of androgen-sensitive and -insensitive prostate cancer cells and xenografts through luteinizing hormone receptors

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BACKGROUND. We have prepared a conjugate of a lytic peptide (hecate) and a 15-amino acid segment of the β-chain of LH to test the concept that this conjugate will target cancer cells expressing LH receptors. METHODS. Hecate-βLH was added in vitro to cultures of Chinese hamster ovary (CHO) cells with and without LH receptors and to prostate cancer cells in the presence or absence of steroids, follicle-stimulating hormone (FSH), epidermal growth factor (EGF), or βLH. PC-3 xenografts were established in male athymic nude mice and treated once a week for 3 weeks with hecate-βLH via the lateral tail vein. RESULTS. The conjugate showed concentration-dependent toxicity for the following prostate cancer cell lines: BRF 41 T>DU145>PC-3>LNCaP, according to their LH receptor capacities. Steroid removal reduced sensitivity to the drug in a reversible manner. Hecate-βLH reduced the tumor burden in the nude mice from 60 to 12.5 mg/g body weight. CONCLUSION. We conclude that the hecate-βLH conjugate selectively kills androgen-dependent and-independent prostate cancer cells both in vivo and in vitro; its toxicity depends on the number of LH receptor sites present. © 2001 Wiley-Liss, Inc.

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