The soybean-derived peptide lunasin inhibits non-small cell lung cancer cell proliferation by suppressing phosphorylation of the retinoblastoma protein
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Elizabeth J. McConnell1, Bharat Devapatla2, Kavitha Yaddanapudi2,3 and Keith R. Davis1,2,4
1 Owensboro Cancer Research Program, Mitchell Memorial Cancer Center, Owensboro, Kentucky
2 James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky
3 Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky
4 Department of Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, Kentucky
Keith R. Davis, email:
Keywords: bioactive peptides, lunasin, lung cancer, cell cycle regulation
Received: November 25, 2014 Accepted: December 27, 2014 Published: December 31, 2014
Lunasin, a soybean bioactive peptide, has both chemopreventive and chemotherapeutic activities. The aim of this study was to determine the chemotherapeutic potential of lunasin against human lung cancer. Treatment of non-small cell lung cancer (NSCLC) cells with highly purified soybean-derived lunasin caused limited, cell-line specific anti-proliferative effects on anchorage-dependent growth whereas two normal bronchial epithelial cell lines were unaffected. Lunasin’s antiproliferative effects were potentiated upon utilization of anchorage-independent conditions. Furthermore, NSCLC cell lines that were unaffected by lunasin in anchorage-dependent assays exhibited a dose-dependent inhibition in colony formation or colony size. Mouse xenograft studies revealed that 30 mg lunasin/kg body weight per day decreased NSCLC H1299 tumor volume by 63.0% at day 32. Mechanistic studies using cultured NSCLC H661 cells showed that lunasin inhibited cell cycle progression at the G1/S phase interface without inducing apoptosis. Immunoblot analyses of key cell-cycle proteins demonstrated that lunasin altered the expression of the G1 specific cyclin-dependent kinase complex components, increased levels of p27Kip1, reduced levels of phosphorylated Akt, and ultimately inhibited the sequential phosphorylation of the retinoblastoma protein (RB). These results establish for the first time that lunasin can inhibit NSCLC proliferation by suppressing cell-cycle dependent phosphorylation of RB.
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