Effects of Isoliquiritigenin (ISL) and [6]-Gingerol on Invasive Bladder Cancer
Sanjna Das, High School; Travis Sullivan, MS; Kimberly Rieger-Christ, PhD
Lahey Hospital & Medical Center, Burlington, MA
BACKGROUND: It is estimated that nearly 80,000 cases of bladder cancer will be diagnosed in the United States in 2017. Treatment for invasive bladder cancer, an advanced stage of this disease, often requires the removal of the entire bladder in a complicated surgery and/or treatments that exert undesirable side effects on the patient. This project addresses the potential of ISL (Isoliquiritigenin), which comes from licorice, and [6]-Gingerol, which is derived from ginger, to inhibit bladder cancer metastasis, thereby reducing the adverse effects posed by other treatments as well as the need for bladder removal and further addresses potential molecular mechanisms that may underlie the effects observed. There is currently very limited literature on the role of both compounds in the context of bladder cancer.
METHODS: ISL and [6]-Gingerol were used to treat UMUC3 and T24, two invasive bladder cancer cell lines, upon which the effects of these compounds were observed and analyzed through an MTT assay, which measures cell proliferation, and migration assays, which reveal cellular migration rates. Differential gene and protein expression were then analyzed in only ISL-treated cells with a real-time PCR array, assessing the expression levels of genes that have been implicated in invasive bladder cancer. Subsequently, relative protein levels were measured by Western Blot analysis. Differential lncRNA expression was measured in ISL-treated cells using a real-time PCR array, which measured lncRNA expression levels of genes implicated in cancer. Finally, potential pathways and proteins linked to ISL-based effects were investigated through literature searches.
RESULTS: The MTT and migration assays revealed that proliferation and migration both decreased in the licorice- and ginger-treated cells. Additionally, changes in cell morphology observed through microscopy, of the treated cells compared to controls, demonstrated that treated cells exhibited signs of blebbing (formation of vesicles), a process that has been shown to precede apoptosis. Moreover, the PCR and Western Blot revealed that specific genes and proteins that have been implicated in bladder cancer, namely ACTA2, EZH2, MMP-2, and MMP-9, were downregulated following treatment with ISL. The real-time lncRNA assay, in conjunction with a literature search, revealed that changes in the expression of several lncRNA, including RP11-363E7.4, BCAR4, FOXP4-AS1, and NEAT1, may contribute to the anti-invasive effects produced in the ISL-treated cells, since these lncRNAs have been implicated in cancer-causing processes.
CONCLUSIONS:
There is sufficient evidence to conclude that ISL and [6]-Gingerol have the potential to decrease characteristics associated with bladder cancer metastasis, and that key genes and lncRNAs such as ACTA2, EZH2, FOXP4-AS1, and NEAT1 may play a role in producing the effects observed in the ISL-treated cells. Further research may lead to the identification of novel treatment targets, new therapeutics and improvements in patient morbidity and mortality.
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