Modulation of POPDC1 Expression by Phenothiazine and Trifluoperazine Suppress Colon Cancer Growth and Migration.

OBJECTIVE: The aim of this study was to investigate the effects of CaM antagonist, PTZ, and TFP on cell proliferation and migration of colon cancer cells and its impact on POPDC protein expression. METHODS: The 50% inhibitory concentration (IC50) of PTZ and TFP in SW1116, SW480, HCT-15, and COLO205 colon cancer cell lines are measured using MTT. Western blot and immunocytochemistry were used to determine the expression of PCNA, cyclin D1 (CD1), and POPDC proteins. Cell migration was observed using a scratch wound-healing assay. RESULTS: Treatment with PTZ and TFP inhibited colon cancer cells growth in a dose-dependent manner. PTZ and TFP significantly inhibited the activation of proliferation markers, PCNA and CD1, and the migration of colon cancer cells. Furthermore, POPDC protein was significantly suppressed in all cell types of colon cancer, particularly in SW480. Finally, the CaM antagonist upregulates the POPDC1 expression in colon cancer cells. CONCLUSION: These findings suggest that CaM antagonists suppress colon cancer cells proliferation via downregulation of CD1 and PCNA. In addition, POPDC protein could be used as a biomarker in colon cancer, and CaM antagonist could be used to regulate POPDC1 expression. This study suggests that targeting POPDC1 with CaM inhibition could be a potential therapeutic strategy for colon cancer treatment. 
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Genotype-Phenotype Study of ß-Thalassemia Patients in Sabah.

ß-thalassemia is a serious public health problem in Sabah due to its high prevalence. This study aimed to investigate the effects of different types of ß-globin gene mutations, coinheritance with α-globin gene mutations, XmnI-Gγ, and rs368698783 polymorphisms on the ß-thalassemia phenotypes in Sabahan patients. A total of 111 patients were included in this study. The sociodemographic profile of the patients was collected using a semi-structured questionnaire, while clinical data were obtained from their medical records. Gap-PCR, ARMS-PCR, RFLP-PCR, and multiplex PCR were performed to detect ß- and α-globin gene mutations, as well as XmnI-Gγ and rs368698783 polymorphisms. Our data show that the high prevalence of ß-thalassemia in Sabah is not due to consanguineous marriages (5.4%). A total of six different ß-globin gene mutations were detected, with Filipino ß°-deletion being the most dominant (87.4%). There were 77.5% homozygous ß-thalassemia patients, 16.2% compound heterozygous ß-thalassemia patients, and 6.3% ß-thalassemia/Hb E patients. Further evaluation on compound heterozygous ß-thalassemia and ß-thalassemia/Hb E patients found no concomitant α-globin gene mutations and the rs368698783 polymorphism. Furthermore, the XmnI-Gγ (-/+) genotype did not demonstrate a strong impact on the disease phenotype, as only two of five patients in the compound heterozygous ß-thalassemia group and two of three patients in the ß-thalassemia/Hb E group had a moderate phenotype. Our findings indicate that the severity of the ß-thalassemia phenotypes is closely related to the type of ß-globin gene mutations but not to the XmnI-Gγ and rs368698783 polymorphisms.