The AhR is involved in the regulation of LoVo cell proliferation through cell cycle-associated proteins

• Published in: Cell biology international 2016-05, Vol.40 (5), p.560-568
• Main Authors: Yin, Jiuheng, Sheng, Baifa, Han, Bin, Pu, Aimin, Yang, Kunqiu, Li, Ping, Wang, Qimeng, Xiao, Weidong, Yang, Hua
• Format: Article
• Language: English
• Subjects: 2-b) carbazole (FICZ; 6-formylindolo; 6‐formylindolo (3, 2‐b) carbazole (FICZ); Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; aryl hydrocarbon receptor (AhR); Carbazoles - pharmacology; Cell cycle; Cell Cycle Proteins - metabolism; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell Survival - physiology; Cyclin D1 - drug effects; Cyclin D1 - genetics; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP1A1 - metabolism; G1 arrest; G1 Phase Cell Cycle Checkpoints - drug effects; Humans; Kinases; Membrane Proteins - metabolism; Phosphorylation; proliferation; Receptors, Aryl Hydrocarbon - agonists; Receptors, Aryl Hydrocarbon - antagonists & inhibitors; Receptors, Aryl Hydrocarbon - metabolism; Signal Transduction - drug effects
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1002/cbin.10592

Some ingredients in foods can activate the aryl hydrocarbon receptor (AhR) and arrest cell proliferation. In this study, we hypothesized that 6‐formylindolo [3, 2‐b] carbazole (FICZ) arrests the cell cycle in LoVo cells (a colon cancer line) through the AhR. The AhR agonist FICZ and the AhR antagonist CH223191 were used to treat LoVo cells. Real‐time PCR and Western blot analyses were performed to detect the expression of the AhR, CYP1A1, CDK4, cyclinD1, cyclin E, CDK2, P27, and pRb. The distribution and activation of the AhR were detected with immunofluorescence. A 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) assay and flow cytometric analysis were performed to measure cell viability, cell cycle stage, and apoptosis. Our results show that FICZ inhibited LoVo cell proliferation by inducing G1 cell cycle arrest but had no effect on epithelial apoptosis. Further analysis found that FICZ downregulated cyclinD1 and upregulated p27 expression to arrest Rb phosphorylation. The downregulation of cyclinD1 and upregulation of p27 were abolished by co‐treatment with CH223191. We conclude that the AhR, when activated by FICZ (an endogenous AhR ligand), can arrest the cell cycle and block LoVo cell proliferation.