6-Shogaol Suppresses 2-Amino-1-Methyl-6-Phenylimidazo [4,5-b] Pyridine (PhIP)-Induced Human 786-O Renal Cell Carcinoma Osteoclastogenic Activity and Metastatic Potential.

I-Jeng Yeh,Szu-Chia Chen,Po-Lin Kuo,Chih-Hsing Hung,Meng-Chi Yen,Yen-Hung Wu

doi:10.3390/nu11102306

Abstract

2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) which can be detected in processed meats and red meats, is a potential carcinogen for renal cell carcinoma (RCC). Approximately 30% of patients with metastatic RCC have bone metastases, and the prognosis of RCC with bone metastases is poor. Thus, the aim of the present study was to investigate whether PhIP induced bone metastases and to develop novel therapeutic agents. Our data revealed that PhIP pre-treatment increased the production of parathyroid hormone-related protein (PTHrP) in human 786-O renal cell carcinoma cells. Subsequently, the cultures of human osteoblasts with PhIP-stimulated condition medium of 786-O increased the expression of the macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL), and decreased the expression of osteoprotegerin (OPG). In addition, PhIP-mediated PTHrP up-regulated as well as increased IL-8 secretion in 786-O cells, and then contributed to 786-O-mediated bone resorption. Furthermore, 6-shogaol, which is an active ingredient in ginger, showed suppressive effects on PhIP-mediated bone resorption. In summary, this is the first study to demonstrate that PhIP pre-treatment increases the stimulatory effect of human renal cell carcinoma 786-O on osteoclastogenesis activity directly by PTHrP. In addition, 6-shogaol treatment reverses PhIP-mediated bone resorption. It suggests that 6-shogaol treatment results in bone resorption activity in the RCC model in vitro.

Highlights

Ginger (Zingiber officinale) is distributed throughout the tropical and subtropical regions [1].It is used in cooking but as a medical plant in South East Asia and other countries [1,2], and since ancient times, it has been applied to treat a range of diseases [3,4]
Since the PhIP is a potential carcinogen within processed red meat, this study aimed to evaluate whether PhIP-stimulated renal cell carcinoma (RCC)
The present study shows that PhIP pre-treatment up-regulates the parathyroid hormone-related protein (PTHrP) expression

Summary

Introduction

Ginger (Zingiber officinale) is distributed throughout the tropical and subtropical regions [1]. It is used in cooking but as a medical plant in South East Asia and other countries [1,2], and since ancient times, it has been applied to treat a range of diseases [3,4]. Carbohydrates (50–70%), lipids (3–8%), terpenes, and phenolic compounds are four major constituents of ginger [5]. 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is an abundant heterocyclic aromatic amine that can be found in processed meats and red meats [16]. The International Agency for Research on Cancer has classified processed meats and red meats as carcinogenic and probably carcinogenic to humans respectively [17]. PhIP causes prostate, colon and mammary cancers in rats [18,19]

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