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Silk fibroin peptide suppresses proliferation and induces apoptosis and cell cycle arrest in human lung cancer cells

Authors: Mei-sa Wang1, Yi-bo Du1, Hui-ming Huang2, Zhong-ling Zhu1, Shuang-shuang Du1, Shao-yong Chen2, Hong-ping Zhao2, Zhao Yan1
1 Department of Clinical Pharmacology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
2 Institute of Biomechanics and Medical Engineering, Tsinghua University, Beijing 100084, China
Correspondence to: Hong-ping Zhao: zhaohp@mail.tsinghua.edu.cn, Zhao Yan: yanzhaopaper@163.com,
DOI: 10.1038/s41401-018-0048-0
Received: 10 October 2017
Accepted: 20 May 2018
Advance online: 19 June 2018

Abstract

Silkworm cocoon was recorded to cure carbuncle in the Compendium of Materia Medica. Previous studies have demonstrated that the supplemental silk protein sericin exhibits anticancer activity. In the present study, we investigated the effects of silk fibroin peptide (SFP) extracted from silkworm cocoons against human lung cancer cells in vitro and in vivo and its possible anticancer mechanisms. SFP that we prepared had high content of glycine (~ 30%) and showed a molecular weight of ~ 10 kDa. Intragastric administration of SFP (30 g/kg/d) for 14 days did not affect the weights, vital signs, routine blood indices, and blood biochemical parameters in mice. MTT assay showed that SFP dose-dependently inhibited the growth of human lung cancer A549 and H460 cells in vitro with IC50 values of 9.921 and 9.083 mg/mL, respectively. SFP also dose-dependently suppressed the clonogenic activity of the two cell lines. In lung cancer H460 xenograft mice, intraperitoneal injection of SFP (200 or 500 mg/kg/d) for 40 days significantly suppressed the tumor growth, but did not induce significant changes in the body weight. We further examined the effects of SFP on cell cycle and apoptosis in H460 cells using flow cytometry, which revealed that SFP-induced cell cycle arrest at the S phase, and then promoted cell apoptosis. We demonstrated that SFP (20−50 mg/mL) dose-dependently downregulates Bcl-2 protein expression and upregulates Bax protein in H460 cells during cell apoptosis. The results suggest that SFP should be studied further as a novel therapeutic agent for the treatment of lung cancer.
Keywords: silk fibroin peptide lung cancer cells cell apoptosis anti-cancer

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