Abstract

Indole-3-carbinol (I3C) is an active component of cruciferous vegetables and has been shown to markedly inhibit the growth of a variety of tumors. However, the role of I3C in nasopharyngeal carcinoma (NPC) remains unclear. Thus, the aim of the present study was to investigate the inhibition of NPC cells by I3C in vitro and in vivo. The human CNE2 NPC cell line was treated with various concentrations (0, 100, 200 and 300 μM) of I3C and analysis of cell proliferation after 0, 24, 48 and 72 h, apoptosis after 48 h and expression levels of phosphatidylinositol 3-kinase (PI3K)/Akt pathway-associated proteins in vitro was performed. BALB/c nude mice were divided into the following groups: Prevention, treatment and control. In vivo, all the nude mice were inoculated with CNE2 NPC cells and the mice in the prevention and treatment groups were administered a diet containing 0.5% I3C prior to and following inoculation, respectively. The tumoricidal effect of I3C was investigated in the nude mice. After eight weeks, the expression levels of PI3K/Akt pathway-associated proteins were analyzed in the tumors from the nude mice in each group. The results demonstrated that with increasing I3C concentrations, cell proliferation decreased and apoptosis increased significantly. In addition, the expression levels of PI3K/Akt pathway-associated proteins decreased. In the animal experiments, the prevention and treatment groups developed smaller tumors and the expression levels of PI3K/Akt pathway-associated proteins were reduced when compared with those in the control group. In addition, very few changes to the heart, liver and kidney tissues were observed with hematoxylin and eosin staining in all the groups. Therefore, the results of the present study indicated that I3C inhibited the growth of NPC cells and induced apoptosis effectively in vivo and in vitro. The underlying mechanism may be that I3C suppresses the PI3K/Akt pathway.

Highlights

  • In nasopharyngeal carcinoma (NPC), tumors originate from the epithelial cells that cover the surface of the nasopharynx

  • In order to demonstrate that the final concentration of dimethyl sulfoxide (DMSO) did not affect the NPC cells, CNE2 cells cultured in complete medium alone, without exposure to I3C or DMSO (

  • I3C is extracted from cruciferous vegetables by the hydrolysis of glucosinolates [7]

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Summary

Introduction

In nasopharyngeal carcinoma (NPC), tumors originate from the epithelial cells that cover the surface of the nasopharynx. Despite novel advances in radiotherapy, chemotherapy and gene‐targeting agents, the overall survival rate of patients with aggressive phase NPC remains low [4]. Epidemiological studies have indicated that the intake of broccoli, cauliflower and other cruciferous vegetables can significantly reduce the incidence of numerous types of cancer, including bladder, pancreas, colon, lung and stomach [5,6]. A number of studies have demonstrated that I3C induces cell cycle arrest at the G1 phase in cancer cells [9,10], promotes apoptosis [9,10,11] and prevents tumor invasion and metastasis [11]. I3C has been shown to promote cell cycle arrest by downregulating cyclin‐proteins, including cyclin D1 and E. IC3 has been hypothesized to induce apoptosis by mechanisms that depend on the downregulation of the antiapoptotic genes Bcl‐2, Bcl‐xL and survivin, as well as by enhancing the expression of Bax and by functionally activating caspase‐3 and 9 [10,11,12,13]

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