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Cancer Lett. 1999 Mar 1;136(2):177-85.

Effects of bombesin on methadone-induced apoptosis of human lung cancer cells.

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1
Division of Surgical Oncology, Oregon Health Sciences University, Portland 97201-3098, USA.

Abstract

The therapeutic opioid methadone, used to treat cancer pain and opioid addiction, is also a potent inducer of apoptosis in human lung cancer cells, thereby inhibiting their growth. However, in contrast to its central nervous system (CNS) actions, this effect appears to be mediated through a non-opioid mechanism involving bombesin, an autocrine growth-stimulatory factor that plays a central role in the early events of pulmonary carcinogenesis. Exposure of 'variant' small cell lung carcinoma (SCLC) and non-SCLC cells, which secrete low concentrations (< 0.01 pmol/mg protein) of bombesin, to nanomolar concentrations of methadone resulted in increased levels of mitogen-activated protein (MAP) kinase phosphatases and inactivation of MAP kinase, suppression of the bcl-2 protein, and induction of apoptosis. These effects of methadone were reversed by the addition of bombesin to the culture medium, at concentrations of < 1 microM, and 'classic' SCLC cells, which secrete high concentrations of bioactive bombesin (> 6 pmol/mg protein), were found not to respond to methadone. Thus, methadone's effectiveness is dependent upon the concentration of bioactive bombesin secreted by lung cancer cells. Methadone treatment suggests a novel therapeutic approach for patients presenting 'variant' SCLC and non-SCLC morphologies, since they respond less to conventional therapy.

PMID:
10355747
DOI:
10.1016/s0304-3835(98)00335-8
[Indexed for MEDLINE]

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