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

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 IC 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.

Silk peptide treatment potentiates natural killer cell activityin vitroand induces natural killer cell maturation and activation in mouse splenocytes

“…Silk protein has also been proposed to be a bioactive substance, and has shown efficacy in reducing blood pressure and treating atopic dermatitis, as well as exhibiting antitumor activity, promoting insulin release, and enhancing innate immune responses (Igarashi et al 2006;Teramoto et al 2008;Jung et al 2010;Moon et al 2011;Ikegawa et al 2012). More importantly, silk fibroin peptides and silk protein sericin have been shown to inhibit human lung cancer cell proliferation, induce apoptosis, inhibit colorectal tumor formation and exert anticancer effects (Zhaorigetu et al 2001;Kaewkorn et al 2012;Wang et al 2019). Cytolytic activity in the immune system is essential for maintaining health, as it ensures the removal of pathogen-infected and malignantly transformed cells.…”

“…Silk peptide displays diverse bioactivities, such as anti-inflammatory, immune-regulatory, antitumor, antiviral and antibacterial properties (Singh et al 1990;Gotoh et al 2000;Jung et al 2010). Importantly, silk fibroin peptides and silk protein sericin have been reported to inhibit the proliferation of human lung cancer cells, induce apoptosis, inhibit the formation of colorectal tumors and exert anticancer effects against cancer cells (Zhaorigetu et al 2001;Kaewkorn et al 2012;Wang et al 2019).…”

Silk fibroin safety in the eye: a review that highlights a concern

“…33 In vivo, in mice with lung cancer, tumour growth was suppressed with fibroin. 34 These types of results, taken together with the extensive use of silk suture in the eye without the association of widespread resulting carcinoma, indicate that fibroin may be beneficial in this regard, rather than pathogenic.…”

Self-Assembled Silk Fibroin-Based Aggregates for Delivery of Camptothecin

“…In this sense, we have efficiently synthesized steroids-grafted SF derivatives via carbodiimide-mediated esterification for agrochemicals applications [25]. Furthermore, SF hydrolysate has shown slight antiproliferative effect on MCF-7, A549, and H460 cancer cells [26].…”