Indole-3-carbinol inhibits nasopharyngeal carcinoma cell growth in vivo and in vitro through inhibition of the PI3K/Akt pathway

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.

Glycyrrhizic Acid Prevents Diabetic Nephropathy by Activating AMPK/SIRT1/PGC-1α Signaling in db/db Mice

“…These results suggest that AMPK and SIRT1 activate each other and jointly regulate their downstream effector PGC-1 α in mesangial cells [ 42 , 43 ]. High glucose levels can prevent mesangial cells from transitioning from G1 to S phase, reduce the proportion of cells in G1 phase, increase the proportion of cells in S phase, and promote DNA synthesis and cell proliferation [ 44 ]. Consistent with our results, several recent studies have demonstrated that adiponectin [ 45 ] or AICAR [ 46 ] protect renal podocytes and decrease albuminuria in diabetic animals by decreasing oxidative stress and apoptosis via a mechanism involving the activation of AMPK.…”

Phytochemicals and PI3K Inhibitors in Cancer—An Insight

“…According to their results, as the concentration of I3C increased, in PI3K/Akt pathway associated proteins levels and cell proliferation was decreased while there was an increase in apoptosis. Also in the prevention and treatment groups of mice, there was the development of small tumors and also the levels of PI3K/Akt pathway proteins were reduced (Mao et al, 2014 ).…”

Genome-scale CRISPR-Cas9 knockout screening in nasopharyngeal carcinoma for radiosensitive and radioresistant genes

“…Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs on the top and lateral wall of nasopharyngeal cavity [1] . The tumor originates from the epithelial cells covering the nasopharyngeal surface [2] . NPC is a geographically relevant tumor with a particular global distribution and complex etiology, with higher incidence in Southern China, Southeast Asian countries, Northern and Northeastern Africa, Alaska of the United States, and Western Canada [3] .…”