Abstract. Simvastatin is a low density lipoprotein-lowering drug that is widely used to prevent and treat cardiovascular disease by inhibiting the mevalonate pathway. Simvastatin also exhibits inhibitory effects on a number of types of cancer. In the present study, the effects of simvastatin on the activity of doxorubicin in the breast cancer MCF-7 cell line, and the mechanisms by which this interaction occurs were investigated. The effect of simvastatin and doxorubicin treatment, alone and in combination, on the growth of MCF-7 cells was evaluated by a sulforhodamine B and colony formation assay. To delineate the mechanisms of cell death, the following parameters were measured: Reactive oxygen species (ROS) production using the fluorescence probe dihydroethidium; caspase 3 activity by the fluorometry method; gene expression by quantitative polymerase chain reaction; and apoptotic-and proliferative-related protein levels by western blotting. MCF-7 cell proliferation was significantly suppressed by 24-48 h treatment with simvastatin alone. Doses of 10-50 µM simvastatin also enhanced the cytotoxicity of doxorubicin against MCF-7 cells in a dose-dependent manner, and decreased the colony-forming ability of MCF-7 cells. Simvastatin alone or in combination with doxorubicin significantly increased ROS levels. Combination treatment significantly decreased expression of the cell cycle regulatory protein Ras-related C3 botulinum toxin substrate 1 and numerous downstream proteins including cyclin-dependent kinase (Cdk) 2, Cdk4 and Cdk6. Additionally, simvastatin in combination with doxorubicin significantly induced expression of the cyclin-dependent kinase inhibitor p21, increased cytochrome c and caspase 3 expression and reduced cyclin D1 expression. In conclusion, simvastatin acts synergistically with the anticancer drug doxorubicin against MCF-7 cells, possibly through a downregulation of the cell cycle or induction of apoptosis. Although additional studies are required, simvastatin and doxorubicin combination may be a reasonable regimen for the treatment of breast cancer.

Anemia is a major public health problem in many areas of Southeast Asia. Ascertaining anemia and defining its underlying causes is essential for providing appropriate care, management, and establishment of a control program. Limited studies on these have been carried out on people living at the borders of Thailand, Lao PDR, and Cambodia. This cross-sectional study was done in four areas along the borders of Thailand, Lao PDR, and Cambodia. Blood specimens were collected from subjects aged 15–18 years in four districts including Kantharalak, Si Sa Ket province (n = 36), Nam Khun (n = 109), Nam Yuen (n = 98), and Na Chaluai (n = 128), Ubon Ratchathani province, Thailand. RBC parameters were recorded, and serum ferritin (SF) level was measured. Diagnosis of thalassemia and hemoglobinopathies was based on hemoglobin (Hb) and DNA analyses. Measurement of C-reactive protein was performed to exclude false-negative result of iron deficiency. The prevalence of anemia was found to be 25.1%. ID accounted for only 10.5%. Various types of thalassemia were identified in 67.7% of the subjects. The overall prevalence of thalassemia included 3.5% α0-thalassemia, 0.8% β-thalassemia, 47.7% Hb E, and 53.6% α+-thalassemia. The proportions of ID, thalassemia and combined ID and thalassemia among anemic subjects were 6.5%, 66.6%, and 20.4%, respectively. The results indicate that thalassemia and hemoglobinopathies rather than ID are major causes of anemia in Thailand-Lao PDR-Cambodia triangle. This information should prove useful for implementing an anemia control program in the regions.