casein-kinase-ii and Precancerous-Conditions

Hepatocellular carcinoma (HCC), a highly aggressive form of solid tumor, has been increasing in South East Asia. The lack of effective therapy necessitates the introduction of novel chemopreventive strategies to counter the substantial morbidity and mortality associated with the disease. Recently, we reported that dimethoxy flavone (DMF), a methylated flavone derived from chrysin, significantly suppressed the development of preneoplastic lesions induced by N-nitrosodiethylamine (DEN) in rats, although the mechanism of action was not known. In the present study, we have investigated the effects of DMF administration on gene expression changes related to the inflammation-mediated NF-kB pathway, Wnt pathway and apoptotic mediators in DEN-induced preneoplastic nodules. There was a significant increase in inflammatory markers like cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and a decrease in apoptotic mediators like p53, caspase-3 and bax in DEN-treated rats when compared to the control group. Activation of NF-kB was noticed by an elevated expression of nuclear protein expression of NF-kB and cytoplasmic phospho-IkBαSer(32/36) in the same animals. Likewise, upregulation of canonical Wnt pathway was noticed by elevated expression of nuclear protein levels of phospho-β-cateninThr(393) and cytoplasmic casein kinase-2 (CK2), Dvl2 and cyclin D1 levels, along with a simultaneous decrease in expression of phospho-GSK3β(Ser9). Dietary DMF (100mg/kg) administration inhibited liver nodule incidence and multiplicity by 82% and 78%, respectively. DMF also reversed the activation of NF-kB and Wnt pathway as shown by the decrease in protein expression of several proteins. Results of the present investigation provide evidence that attenuation of Wnt pathway and suppression of inflammatory response mediated by NF-kB could be implicated, in part, in the chemopreventive effects of methylated flavone. Therefore, the present findings hold great promise for the utilization of DMF as an effective chemotherapeutic agent in treating early stages of liver cancer.

Topics: Animals; Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; Carcinoma, Hepatocellular; Casein Kinase II; Caspase 3; Cyclin D1; Cyclooxygenase 2; Diethylnitrosamine; Disease Models, Animal; Flavones; Flavonoids; Gene Expression Regulation, Neoplastic; Liver Neoplasms; Male; NF-kappa B; Nitric Oxide Synthase Type II; Precancerous Conditions; Rats; Rats, Wistar; Signal Transduction; Tumor Suppressor Protein p53; Up-Regulation; Wnt Proteins

To investigate the expression of protein kinase CK2 and its relationship with the development, progress, invasion and metastasis of squamous cell carcinoma of larynx (LSCC).. Immunohistochemical SP staining method was used to assess the expression of CK2 in 18 cases of normal laryngeal mucosa, 14 cases of polyp of vocal cord, 11 cases of larynx papilloma and 50 cases of LSCC patients. And RT-PCR was used to detect the expression of CK2alpha mRNA and CK2beta mRNA in 50 cases of LSCG patients. The relationship between CK2alpha and CK2p was evaluated.. The positive expression rate of CK2alpha and CK2beta in normal laryngeal mucosa, polyp of vocal cord and tissues close to carcinoma by 1.0 cm, nonmetastatic lymph nodes were lower than that in tissues close to carcinoma by 0.5 cm and laryngeal papilloma. The positive expression rate of CK2alpha and CK2beta in laryngeal carcinoma and metastatic lymph nodes were the highest among the groups. The expression rate of CK2alpha and CK2beta in tissues of laryngeal carcinoma and metastatic lymph nodes of neck was significantly higher than that of laryngeal papilloma and tissues close to carcinoma by 0.5 cm (P < 0.05). In the group of LSCC, the expression of CK2alpha in G2 and in G3 was significantly higher than that in G1 (P < 0.05). While the age of the patients, TNM stage and lymphatic metastasis didn't change in the expression of CK2alpha obviously. The expression of CK2beta correlates to the differentiation grading and lymphatic metastasis in LSCC patients, but not to the age and TNM stage. The result from RT-PCR was highly consistent with that from immunohistochemical SP staining. There was a positive correlation between the expression of CK2alpha in LSCC patients and that of CK2beta.. The over expression of protein kinase CK2 may be an accelerator to the formation and development of LSCC. Protein kinase CK2 may be one of the predictors for the malignant grade of LSCC. To inhibit the over expression might be new therapeutic methods for LSCC.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Casein Kinase II; Female; Humans; Laryngeal Mucosa; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Staging; Precancerous Conditions