Sepia ink oligopeptide induces apoptosis and growth inhibition in human lung cancer cells

Abstract

// Zhi Zhang 1, * , Lei Sun 2, * , Guoren Zhou 3 , Peng Xie 4 , Jinjun Ye 4 1 Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210000, Jiangsu, China 2 Department of Medical Iconography, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210000, Jiangsu, China 3 Department of Chemotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210000, Jiangsu, China 4 Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210000, Jiangsu, China * These authors contributed equally to this work Correspondence to: Jinjun Ye, email: jinjunyeg@sina.com Guoren Zhou, email: zhouguoren888@126.com Keywords: sepia ink oligopeptide (SIO), lung cancer cell, stable peptide, apoptosis, p53 Received: January 12, 2017      Accepted: February 12, 2017      Published: February 20, 2017 ABSTRACT Sepia ink oligopeptide (SIO), as a tripeptide extracted from Sepia ink, could be used as an inducer of apoptosis in human prostate cancer cells. We designed a cyclo-mimetic peptide of SIO by introducing a disulfide bond to stabilize the native peptide into beta turn structure, and produced a peptide with higher cell permeability and stability. Through labeling an FITC to the N-terminus of the peptide, the cell permeability was examined. Stabilized peptide showed enhanced cellular uptake than linear tripeptide as indicated by flow cytometry and cell fluorescent imaging. The high intracellular delivery of stable SIO could more efficiently inhibit cell proliferation and induce apoptosis. Furthermore, the expression of the anti-apoptotic protein Bcl-2 was down-regulated, whereas pro-apoptotic proteins P53 and caspase-3 were up-regulated by stable SIO. In conclusion, our study is the first to use stable SIO to induce apoptosis in two lung cancer cells A549 and H1299.