Abstract

Context: Lentinus squarrosulus Mont. (Polyporaceae) is an interesting source of diverse bioactive compounds.Objective: This is the first study of the anticancer activity and underlying mechanism of peptides extracted from Lentinus squarrosuls.Materials and methods: Peptides were isolated from the aqueous extract of L. squarrosulus by employing solid ammonium sulphate precipitation. They were further purified by ion-exchange chromatography on diethylaminoethanol (DEAE)-cellulose and gel filtration chromatography on Sephadex G25. Anticancer activity was investigated in human lung cancer H460, H292 and H23 cells cultured with 0–40 μg/mL of peptide extracts for 24 h. Cell viability and mode of cell death were evaluated by MTT and nuclear staining assay, respectively. Western blotting was used to investigate the alteration of apoptosis-regulating proteins in lung cancer cells treated with peptide extracts (0–20 μg/mL) for 24 h.Results: The cytotoxicity of partially-purified peptide extracts from L. squarrosulus was indicated with IC50 of ∼26.84 ± 2.84, 2.80 ± 2.14 and 18.84 ± 0.30 μg/mL in lung cancer H460, H292 and H23 cells, respectively. The extracts at 20 μg/mL induced apoptosis through the reduction of anti-apoptotic Bcl-2 protein (∼0.5-fold reduction) and up-regulation of BAX (∼4.5-fold induction), a pro-apoptotic protein. Furthermore, L. squarrosulus peptide extracts (20 μg/mL) also decreased the cellular level of death receptor inhibitor c-FLIP (∼0.6-fold reduction).Conclusions and discussion: This study provides the novel anticancer activity and mechanism of L. squarrosulus peptide extracts, which encourage further investigation and development of the extracts for anticancer use.

Highlights

  • Lung cancer is currently a leading cause of cancer mortality, worldwide (Siegel et al 2015)

  • This study aimed to evaluate the anticancer activity and the underlying mechanism of peptide extracted from the Thai edible mushroom Lentinus squarrosulus in human lung cancer cells

  • This investigation demonstrated that peptides extracted from L. squarrosulus at concentrations of 1–40 lg/mL significantly decreased viability and induced apoptosis of various human lung cancer cells including H460, H23 and H292 cells

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Summary

Introduction

Lung cancer is currently a leading cause of cancer mortality, worldwide (Siegel et al 2015). An extrinsic apoptosis pathway induced by death ligand binding to its receptor, frequently fails to execute the cancer cells because of the high cellular level of c-FLIP (FLICE-like inhibitory protein), a potent inhibitor for caspase-8 (Wang et al 2008; Safa & Pollok 2011). Taken together, targeting these anti-apoptosis members of the Bcl-2 family and c-FLIP are a promising way to sensitize the cancer cells to apoptosis

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