Abstract
Purpose: To investigate the effect of licochalcone A (LA) on the inhibition of cell proliferation and ERK1/2 phosphorylation in bladder carcinoma cell lines.Methods: Cell viability was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Dye-binding method was used to examine the concentration of proteins. Lymphocytes were extracted from mice and after surface staining were subjected to BD fixation and permeabilization for intracellular staining. Flow cytometry was used to measure cellular fluorescence.Results: MTT results revealed a significant decrease in the proliferation of UM-UC-3, J82 and HT-1197 cell lines on treatment with LA. LA also induced reduction in phosphorylation of ERK1/2 in all three carcinoma cell lines. In the mouse model, licochalcone A treatment via intraperitoneal (ip) administration induced a significant decrease in the level of regulatory T cells (Tregs). Comparison of the mouse interferon-α (IFN-α)-treated and LA-treated groups revealed that LA treatment caused enhancement of cytotoxic T lymphocyte (CTL) activity similar to that of IFN-α. Administration of UM-UC-3 cells in C3H/HeN mice resulted in marked reduction in the counts for splenocytes and CD4+ CD25+ Foxp3+ T (regulatory T cells) cell proportion in LA-treated mice compared to untreated control group.Conclusion: Licochalcone A may be of therapeutic importance for the prevention of bladder carcinoma. However, studies are required to ascertain the compound’s usefulness in this regard.Keywords: Licochalcone A, Bladder carcinoma, Splenocytes, Phosphorylation, Cell proliferation, Interferon
Highlights
Cancer is the leading cause of death in economically developed countries and second leading cause of death in developing countries [1]
The results revealed that licochalcone A treatment inhibits bladder cancer cell proliferation and reduces ERK1/2 phosphorylation
It was observed that licochalcone A suppressed the growth of all the three tested bladder cancer cell lines in a dose-dependent manner (Figure 1)
Summary
Cancer is the leading cause of death in economically developed countries and second leading cause of death in developing countries [1]. Tyrosine kinases mediate the binding of growth factors with their corresponding receptors [8] Chalcones because of their potent biological activities have been the target of interest for the chemists as well as clinicians globally. In the present study the effect of licochalcone A (LA) on bladder carcinoma in human bladder cancer cells and mice model was investigated. The results revealed that licochalcone A treatment inhibits bladder cancer cell proliferation and reduces ERK1/2 phosphorylation. The bladder cancer cell lines, UM-UC-3, J82 and HT-1197 were obtained from The Cell Bank of Type Culture Collection of Chinese Academy of Sciences, Shanghai Institute of Cell Biology (Shanghai, China). The splenocytes were extracted and cultured with mitomycin C (MMC)treated UM-UC-3 cells for 5 days after adding 25 ng/mL IL-2 (Takeda Chemical Industries, Tokyo, Japan). Graph Pad Prism 5 (Graph Pad Software, Inc., San Diego, CA, USA) was used for the analysis of the data
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