Mistletoe lectin inhibits growth of Myc-amplified small-cell lung cancer

Background: Small-cell lung cancer (SCLC) is the deadliest form of lung cancer but lacks targeted therapies. Methods: We studied the effect of the natural product mistletoe lectin (ML) in pre-clinical models of SCLC, focusing on cell lines with amplification of the myc family oncogenes C-myc and N-myc. Results: We found that ML treatment inhibits growth of SCLC cell lines in culture and induces apoptosis. ML treatment also decreases the expression of the amplified myc proteins. Over-expression of either C-myc or N-myc results in enhanced SCLC cell sensitivity to ML. In a mouse xenograft model of SCLC, treatment with ML results in decreased tumor growth over 4 weeks with evidence of increased apoptosis in tumors from treated animals. Conclusion: Overall, our results demonstrate that ML exhibits therapeutic potential in SCLC, that is at least partially dependent on myc protein expression.