Nobiletin inhibits cell growth through restraining aerobic glycolysis via PKA-CREB pathway in oral squamous cell carcinoma.

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.

Curcumin analog EF24 induces apoptosis and downregulates the mitogen activated protein kinase/extracellular signal-regulated signaling pathway in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide. Diphenyldifluoroketone (EF24) is a curcumin analog that has been demonstrated to improve anticancer activity; however, its therapeutic potential and mechanisms in oral cancer remain unknown. In the present study, the effect of EF24 on apoptosis induction and its potential underlying mechanism in the CAL­27 human OSCC cell line was investigated. To achieve this, various concentrations of cisplatin or EF24 were administrated to CAL­27 cells for 24 h, and cell viability, apoptotic DNA fragmentation, and cleaved caspase 3 and 9 levels were evaluated. To investigate the potential underlying mechanism, the levels of mitogen­activated protein kinase kinase 1 (MEK1) and extracellular signal­regulated kinase (ERK), two key proteins in the mitogen­activated protein kinase/ERK signaling pathway, were additionally examined. The results indicated that EF24 and cisplatin treatment decreased cell viability. EF24 treatment increased the levels of activated caspase 3 and 9, and decreased the phosphorylated forms of MEK1 and ERK. Sequential treatments of EF24 and 12­phorbol­13­myristate acetate, a MAPK/ERK activator, resulted in a significant increase of activated MEK1 and ERK, and reversed cell viability. These results suggested that EF24 has potent anti­tumor activity in OSCC via deactivation of the MAPK/ERK signaling pathway. Further analyses using animal models are required to confirm these findings in vivo.

[The curative effects of bone mesenchymal stem cells transplanted into rats with Sjogren's syndrome].

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.