Curcumin Inhibits Non-Small Cell Lung Cancer Cells Metastasis through the Adiponectin/NF-κb/MMPs Signaling Pathway.

Jong-Rung Tsai,Inn-Wen Chong,Jhi-Jhu Hwang,Yu-Jen Cheng,Po-Len Liu,Shah-Hwa Chou,Yung-Hsiang Chen,Jeremy J.W Chen

doi:10.1371/journal.pone.0144462

Abstract

Adipose tissue is now considered as an endocrine organ involved in metabolic and inflammatory reactions. Adiponectin, a 244–amino acid peptide hormone, is associated with insulin resistance and carcinogenesis. Curcumin (diferuloylmethane) is the principal curcuminoid of the popular Indian spice, turmeric. Curcumin possesses antitumor effects, including the inhibition of neovascularization and regulation of cell cycle and apoptosis. However, the effects of adiponectin and curcumin on non-small cell lung cancer (NSCLC) remain unclear. In this study, we evaluated the expression of adiponectin in paired tumors and normal lung tissues from 77 patients with NSCLC using real-time polymerase chain reaction, western blotting, and immunohistochemistry. Kaplan–Meier survival analysis showed that patients with low adiponectin expression ratio (<1) had significantly longer survival time than those with high expression ratio (>1) (p = 0.015). Curcumin inhibited the migratory and invasive ability of A549 cells via the inhibition of adiponectin expression by blocking the adiponectin receptor 1. Curcumin treatment also inhibited the in vivo tumor growth of A549 cells and adiponectin expression. These results suggest that adiponectin can be a prognostic indicator of NSCLC. The effect of curcumin in decreasing the migratory and invasive ability of A549 cells by inhibiting adiponectin expression is probably mediated through NF-κB/MMP pathways. Curcumin could be an important potential adjuvant therapeutic agent for lung cancer in the future.

Highlights

Lung cancer remains the leading cause of cancer-related mortality worldwide and in Taiwan
Using in vitro A549 cell culture and an animal model, we demonstrated the potential role of curcumin for treating lung cancer
Adiponectin expression was not correlated with tumor (T), lymph nodes (N), and stages

Summary

Introduction

Lung cancer remains the leading cause of cancer-related mortality worldwide and in Taiwan. Adiponectin is a potential marker of prostate cancer progression [10] In chondrosarcoma, it mediates the migration of human chondrosarcoma cells by the transcriptional upregulation of alpha2beta integrin and activation of AdipoR receptor, AMPK, p38, and NF-κB pathways [11]. Curcumin can induce cellular apoptosis in non-small cell lung cancer (NSCLC) [23,24]. How to augment currently available chemotherapeutic treatments with adjunctive herbal medicines, which may decrease side effects and toxicity without compromising therapeutic efficacy, has become a popular approach in recent decades Using in vitro A549 cell culture and an animal model, we demonstrated the potential role of curcumin for treating lung cancer. The potential of curcumin as an adjuvant agent in lung cancer treatment will be explored

Results

Discussion

Materials and Methods

Ethics statement