ABSTRACT
BACKGROUND/AIM: Nobiletin is a polymethoxylated flavone enriched in Citrus and is used as an important drug in traditional Chinese medicine for various kinds of diseases. Among its multiple functions, it has shown that nobiletin inhibits proliferation of various cancer cells. However, it is unclear whether nobiletin inhibits the growth of oral squamous cell carcinoma (OSCC) cells. MATERIALS AND METHODS: We explored the antitumor effects of nobiletin in TCA-8113 and CAL-27 oral squamous cells. The Cell Counting Kit-8 (CCK8) assay was used to measure cell vitality. Flow cytometry was performed to measure the number of cells in the various phases of the cell cycle. PCR and Western blot were applied to determine mRNA and protein expression, respectively. RESULTS: Nobiletin inhibited proliferation of TCA-8113 and CAL-27 cells via inducing cell cycle arrest at the G1 phase. In addition, the levels of phosphorylated-PKA and phosphorylated-CREB were reduced in nobiletin-treated TCA-8113 and CAL-27 cells. Importantly, our results showed that nobiletin treatment resulted in impaired mitochondrial function and altered glucose consumption, and pyruvate and lactate production. Lastly, nobiletin was found to inhibit the generation of xenografts in vivo. Interestingly, administration of 50 µmol/L Sp-cAMP, a potent PKA activator, rescued all phenotypes caused by nobiletin. CONCLUSIONS: Nobiletin inhibits OSCC cell proliferation in a mitochondria-dependent manner, indicating that it may have a promising role in cancer treatment and attenuation of drug resistance.
ABSTRACT
PURPOSE: To study the curative effects, survival rate, migration and differentiation of bone mesenchymal stem cells (BMSCs) transplanted into rats with Sjogren's syndrome. METHODS: Model of Sjogren's syndrome was created in rats. BMSCs were isolated and cultured by using the preceding method. Then the pretreated BMSCs were identified and labeled by enhanced green fluorescent protein. BMSCs marked with enhanced green fluorescent protein (EGFP) or PBS were injected into the SMG of the Sjogren's syndrome rats via open surgery.Total static saliva flow rate was determined in rats. The daily amount of water in the normal group, the model group, the model treatment group and the model treatment control group was recorded. The survival rate, migration and differentiation of the BMSCs transplanted in the treatment group under fluorescence microscope was recorded. Student's t test was used for data analysis using SPSS 12.0 software package. RESULTS: Compared with the model treatment control group, the total static saliva flow rate of the model treatment group increased significantly, and the water they drank decreased significantly (P<0.05). In addition, BMSCs were distributed along the injection tract mostly in the first week,then BMSCs were mainly distributed in the stroma between the acinar in the second week and were distributed over other areas four weeks later. Immunohistochemical staining of amylzyme was not observed at the first week after transplantation. And at the 8th week the expression of amylzyme in the cytoplasm of the transplanted BMSCs was observed by immunohistochemical only in the model treatment group. CONCLUSION: Transplantation of BMSCs has certain treatment effect on Sjogren's syndrome.
