Benzyl Isothiocyanate Inhibits Prostate Cancer Development in the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) Model, Which Is Associated with the Induction of Cell Cycle G1 Arrest.

Han Cho,Hyerim Song,Do Lim,Yoon Oh,Young-Hee Kang,Gyoo Kwon,Zunnan Huang,Jung Park,Ki Lee,Zigang Dong,Ji Kim

doi:10.3390/ijms17020264

Abstract

Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has been shown to have anti-tumor properties. In the present study, we investigated whether BITC inhibits the development of prostate cancer in the transgenic adenocarcinoma mouse prostate (TRAMP) mice. Five-week old, male TRAMP mice and their nontransgenic littermates were gavage-fed with 0, 5, or 10 mg/kg of BITC every day for 19 weeks. The weight of the genitourinary tract increased markedly in TRAMP mice and this increase was suppressed significantly by BITC feeding. H and E staining of the dorsolateral lobes of the prostate demonstrated that well-differentiated carcinoma (WDC) was a predominant feature in the TRAMP mice. The number of lobes with WDC was reduced by BITC feeding while that of lobes with prostatic intraepithelial neoplasia was increased. BITC feeding reduced the number of cells expressing Ki67 (a proliferation marker), cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 in the prostatic tissue. In vitro cell culture results revealed that BITC decreased DNA synthesis, as well as CDK2 and CDK4 activity in TRAMP-C2 mouse prostate cancer cells. These results indicate that inhibition of cell cycle progression contributes to the inhibition of prostate cancer development in TRAMP mice treated with BITC.

Highlights

The American Cancer Society estimated that prostate cancer was the second most important cause of cancer death, surpassed by lung cancer and the most frequently diagnosed cancer in American men [1]
In order to examine whether Benzyl isothiocyanate (BITC) administration suppresses prostate cancer development, we gavage-fed 5-week old transgenic adenocarcinoma mouse prostate (TRAMP) mice and their non-transgenic littermates with BITC for 19 weeks
The levels of creatinine and activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the sera were not increased by BITC administration (Table 2)

Summary

Introduction

The American Cancer Society estimated that prostate cancer was the second most important cause of cancer death, surpassed by lung cancer and the most frequently diagnosed cancer in American men [1]. Since prostate cancer occurs mainly in older men, the prevention of prostate cancer during earlier life could be an effective way to reduce the rate of prostate cancer-related deaths. Epidemiological evidence indicates that dietary intake of cruciferous vegetables decreases the risk of prostate cancers [3]. Singh and Singh proposed that cancer prevention with dietary isothiocyanates (ITCs) is ready for clinical translational research [4]. Benzyl isothiocyanate (BITC) is one of the components in cruciferous vegetables with anticancer effects, which have been attributed to an ITC functional group. BITC was reported to induce apoptosis associated with Bcl-xL phosphorylation [9]. BITC was reported to induce protective autophagy in human prostate cancer cells via inhibition of the mTOR signaling pathway [10]

Methods

Results

Conclusion