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Structural characterization of centipede oligopeptides and capability detection in human small cell lung carcinoma: inducing apoptosis

Author:
Zhao, JingQuan, Yang, Jianmei, Hao, Zerui, An, Yulin, Zhang, Mingqiang, Liu, Jie, Ren, Rongrong, Lin, Dianjie
Source:
RSC advances 2019 v.9 no.19 pp. 10927-10936
ISSN:
2046-2069
Subject:
Scolopendra, apoptosis, caspases, cell lines, cytotoxicity, humans, lung neoplasms, membrane potential, metastasis, mitochondria, mitochondrial membrane, neoplasm cells, oligopeptides, prognosis
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.
Agid:
6368082