Neuropeptides bombesin and calcitonin induce resistance to etoposide induced apoptosis in prostate cancer cell lines

M. Salido, J. Vilches and A. López

Department of Cellular Biology, School of Medicine, University of Cádiz, Spain

Offprint requests to: Dra. M. Salido, Department of Cellular Biology.,School of Medicine, University of Cádiz, Plaza Fragela s/n, 11003 Cádiz, Spain. e-mail: mercedes.salido@uca.es

Summary. Background: Neuroendocrine differentiation in prostatic carcinoma has been related to regulation of proliferation and metastatic potential and correlated with prognosis. More than 80% of prostate carcinomas initially respond to androgen ablation, but most relapse, due to the heterogeneous presence of androgen-dependent and independent clones. The pathways of cellular proliferation and apoptosis are inexorabily linked to minimize the ocurrence of neoplasia, and disfunction of apoptosis is proposed as a pathogenic process in malignant tumors. Androgen-dependent prostatic cancer cells undergo apoptosis after androgen deprivation, but not androgen-independent ones due to a defect in the initiation step. Anyway, they retain the basic cellular machinery to undergo apoptosis. We suggest a possible role of neuroendocrine differentiation in the onset and regulation of apoptosis in prostatic neoplasia. Methods: LNCaP, PC-3 and DU 145 prostatic cancer cell lines were induced to undergo apoptosis after treatment with etoposide alone or plus androgen ablation. We tested the role of neuropeptides bombesin and calcitonin at modulating etoposide induced apoptosis. Results: Etoposide-induced apoptosis in all cancer cell lines was achieved. In LNCaP androgen ablation was also required. Apoptosis is prevented in all three lines when bombesin was added. Calcitonin addition prevents apoptosis in PC-3, LNCaP and in an etoposide dose-dependent way in DU 145. Conclusion: Neuropeptides bombesin and calcitonin can modulate the apoptotic response of prostate cancer cells by inducing resistance to etoposide-induced apoptosis, suggesting that neuropeptides can be used as a target of therapeutical approach in prostatic carcinoma. Histol. Histopathol. 15, 729-738 (2000)

Key words: Apoptosis, Modulation, Neuroendocrine peptides, Prostate carcinoma, Etoposide

DOI: 10.14670/HH-15.729