Abstract

Lung cancer is the most frequent cause of cancer deaths in the world, and smoking is considered as one of the major causes. Small cell lung carcinoma (SCLC) represents a highly malignant and particularly aggressive form, with properties of widespread metastases and poor prognosis. Herein, twenty-five Scolopendra subspinipes mutilans L. Koch Oligopeptides (SSMOs) were isolated and their structures were identified, and the anti-proliferative activity against lung cancer cell lines was evaluated. Results showed that SSMO-5 induced the production of reactive oxygen species (ROS) markedly in NCI-H446 cells. Furthermore, SSMO-5 decreased the mitochondrial membrane potential (MMP) and enhanced the mitochondria-related apoptosis. These results demonstrate that in NCI-H446 cells, the apoptotic and cytotoxic effects of SSMO-5 are mediated by the intrinsic mitochondria-mediated apoptotic pathway, which in turn causes the activation of caspases and increases Bax expression, while decreases Bcl-2 and Bcl-xL expressions and regulates the interaction of p53/MDM2. In conclusion, a ROS-mediated mitochondrial pathway plays an important role in the process of SSMO-5-induced apoptosis against SCLC.

Highlights

  • Lung cancer is a leading cause of cancer death worldwide, which is classi ed into two major groups, small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC).[1]

  • We showed that subspinipes mutilans L. Koch Oligopeptides (SSMOs)-5, a novel Scolopendra subspinipes mutilans oligopeptide, is effective in inducing cell apoptosis in the SCLC NCI-H446 cells

  • The SSMO-5 effectively inhibited the growth of NCI-H446 cells in a dose-dependent manner

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Summary

Introduction

Lung cancer is a leading cause of cancer death worldwide, which is classi ed into two major groups, small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC).[1]. Pharmaceutical peptides have been recognized for years with their special biological properties of small molecular weight, endogenous targets, easy to penetrate tumor cells, signi cant immune response, and inhibiting tumor angiogenesis, tumor growth and metastasis, and such anti-tumor peptides have become a hot spot in cancer treatments.[4] Researchers have screened dozens of anti-tumor peptides and have proved that they can effectively inhibit the growth or occurrence of tumors. Thymopentin can promote the reconstruction of immune function, inhibit the proliferation, spread and metastasis of tumor, reduce the side effects and improve the quality of life. Both medicinal herbs and animals provide a signi cant peptide resource, which can be explored for potential anticancer agents.[5,6,7]

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