Opioids induce while nicotine suppresses apoptosis in human lung cancer cells

R. Maneckjee, J. D. Minna

Research output: Contribution to journalArticlepeer-review

196 Scopus citations


Previously, we have shown that opioids acting via specific receptors inhibit the growth of human lung cancer cells while nicotine, acting through nicotinic acetylcholine receptors, reverses this inhibition. Therefore, we studied the role of apoptosis in these processes. Treatment of human lung cancer cells with 0.1-1 μM morphine or methadone resulted in morphological changes and cleavage of DNA into nucleosome-sized fragments characteristic of apoptosis. Quantitation of DNA fragmentation showed that a dose-dependent increase occurred within 2 h of opioid treatment and was blocked by the antagonist naloxone. The apoptotic effect of opioids was suppressed by nicotine, while the nicotinic acetylcholine receptor antagonists, hexamethonium and decamethonium, reversed this suppression. In contrast, sphingosine, a protein kinase C inhibitor, caused significant DNA fragmentation which was not suppressed by nicotine. Unexpectedly, the combination of hexamethonium and opioids or hexamethonium and nicotine stimulated apoptosis. We found that nicotine, like phorbol 12-myristate 13- acetate, increased total protein kinase C (PKC) activity, while morphine and sphingosine decreased PKC activity, and nicotine reversed morphine inhibition of PKC activity. In contrast, methadone unexpectedly increased PKC activity. These results indicate that engagement of opioid receptors in human lung cancer cells induces apoptosis, while engagement of nicotine receptors suppresses apoptosis, which in some cases appear to be working through a PKC pathway. They also suggest complexities in the system where blockade of C6 or C10 nicotinic receptors can lead to facilitation of apoptosis. These findings suggest new strategies for treatment and prevention of cancer using opioids or nicotine receptors antagonists and are consistent with the idea that nicotine functions as a tumor promoter.

Original languageEnglish (US)
Pages (from-to)1033-1040
Number of pages8
JournalCell Growth and Differentiation
Issue number10
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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