The soybean-derived peptide lunasin inhibits non-small cell lung cancer cell proliferation by suppressing phosphorylation of the retinoblastoma protein.

Elizabeth J Mcconnell,Bharat Devapatla,Keith R Davis,Kavitha Yaddanapudi

doi:10.18632/oncotarget.3080

Elizabeth J Mcconnell, Bharat Devapatla + Show 2 more

Open Access

https://doi.org/10.18632/oncotarget.3080

Copy DOI

Journal: Oncotarget	Publication Date: Dec 31, 2014
Citations: 76	License type: cc-by

Affiliation: Owensboro Health, University of Louisville

Abstract

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.

Highlights

Lung cancer remains the number one cause of cancer-related deaths among both men and women in the United States, with an estimated 159,260 deaths and 224,210 new diagnoses being expected in 2014
While greater than 90% of the incidence of small cell lung cancer is the result of unchecked proliferation due to acquired mutations in RB1, development of Non-small cell lung cancer (NSCLC) is attributed to the accumulation of mutations in genes involved in the upstream regulation of the retinoblastoma protein (RB), such as TP53, CCND1, and CDKN2A (encoding the cyclin-dependent kinase inhibitor (CDKI) p16INK4a) [2]
Lunasin treatment of other NSCLC cell lines (H1299, H460 and A549) and normal bronchial epithelial (NBE) cell lines (HBE135-E6E7 and BEAS-2B) resulted in little or no effect when treated over 72 hours (Fig. 1B)

Summary

Introduction

Lung cancer remains the number one cause of cancer-related deaths among both men and women in the United States, with an estimated 159,260 deaths and 224,210 new diagnoses being expected in 2014. Of those diagnosed, approximately 60% will die within a year. [3,4,5,6,7,8,9] epidemiological www.impactjournals.com/oncotarget observations have identified a correlation between high levels of soybean consumption with lowered incidence and mortality due to breast, prostate, colon and lung cancer [5, 10,11,12,13,14,15,16,17] Soy-derived products have received increasing interest due to their purported health benefits, including cardiovascular health, weight management, diabetes, osteoporosis, and cancer prevention. [3,4,5,6,7,8,9] epidemiological www.impactjournals.com/oncotarget observations have identified a correlation between high levels of soybean consumption with lowered incidence and mortality due to breast, prostate, colon and lung cancer [5, 10,11,12,13,14,15,16,17]

Objectives

Results

Conclusion