Antrodia cinnamomea induces anti-tumor activity by inhibiting the STAT3 signaling pathway in lung cancer cells

Tsung-Teng Huang,Ying-Wei Lan,John D Young,Kowit-Yu Chong,Chuan-Mu Chen,David M Ojcius,Jan Martel,Yun-Fei Ko

doi:10.1038/s41598-019-41653-9

Abstract

We examined the effects of an Antrodia cinnamomea ethanol extract (ACEE) on lung cancer cells in vitro and tumor growth in vivo. ACEE produced dose-dependent cytotoxic effects and induced apoptosis in Lewis lung carcinoma (LLC) cells. ACEE treatment increased expression of p53 and Bax, as well as cleavage of caspase-3 and PARP, while reducing expression of survivin and Bcl-2. ACEE also reduced the levels of JAK2 and phosphorylated STAT3 in LLC cells. In a murine allograft tumor model, oral administration of ACEE significantly inhibited LLC tumor growth and metastasis without affecting serum biological parameters or body weight. ACEE increased cleavage of caspase-3 in murine tumors, while decreasing STAT3 phosphorylation. In addition, ACEE reduced the growth of human tumor xenografts in nude mice. Our findings therefore indicate that ACEE inhibits lung tumor growth and metastasis by inducing apoptosis and by inhibiting the STAT3 signaling pathway in cancer cells.

Highlights

Lung cancer is one of the most prevalent cancers and the leading cause of cancer-related mortality worldwide[1]
We examined whether Antrodia cinnamomea ethanol extract (ACEE) produces cytotoxic effects on Lewis lung carcinoma (LLC) and CL1-5 lung cancer cells using the MTT cell viability assay
We observed that ACEE induces apoptosis in lung cancer cells and reduces tumor growth and metastasis in an animal model of allograft tumor in mice

Summary

Introduction

Lung cancer is one of the most prevalent cancers and the leading cause of cancer-related mortality worldwide[1]. Inhibition of STAT3 activation may represent an effective approach to treat lung cancer. A previous study showed that an ethanol extract of the mycelium induces apoptosis of A549 lung cancer cells by down-regulating expression of galectin-1, RhoGDI-α, calpain-1 small subunit and eIF-5A16. An ethanol extract of A. cinnamomea fruiting bodies has been shown to inhibit migration of highly metastatic CL1-5 lung cancer cells by reducing expression of matrix metalloproteinase-2/9 via the mitogen-activated protein kinase (MAPK) and phosphatidylinositiol-3-kinase/Akt signaling pathways[17]. The molecular mechanism of the anti-cancer activity of A. cinnamomea in lung cancer cells has not been studied in detail. We examined the effects and mechanism of action of an Antrodia cinnamomea ethanol extract (ACEE) on lung cancer cells in vitro and in vivo

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