[Show abstract][Hide abstract] ABSTRACT: 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] plays an anticancer role in multiple types of cancer and potentiates the cytotoxic effects of several common chemotherapeutic agents. The hypercalcemia caused by 1,25(OH)2D3 alone or resistance to cisplatin weaken the anticancer effects of vitamin D. Thus, in this study, we aimed to investigate the synergistic effects of 1,25(OH)2D3 and cisplatin on the apoptosis and cell cycle progression of gastric cancer cells. BGC-823 human gastric cancer cells were treated with 1,25(OH)2D3 or cisplatin alone, or a combination of both agents. Cell apoptosis was assessed by TUNEL assay and flow cytometry. The expression of the apoptosis-related proteins, poly(ADP-ribose) polymerase (PARP), Bax, Bcl-2, caspase-3 and caspase-8, was examined using immunoblot analysis. ERK and AKT phosphorylation were examined by immunoblot analysis. The cell cycle distribution was determined by propidium iodide staining and flow cytometric analysis. p21 and p27 protein expression was also examined using immunoblot analysis. Our results revealed that co-treatment with 1,25(OH)2D3 enhanced cisplatin-induced apoptosis and upregulated the expression of Bax, and promoted the cleavage of PARP and caspase-3. The phosphorylation levels of ERK and AKT were reduced following combined treatment with 1,25(OH)2D3 and cisplatin. The percentage of cells in the G0/G1 phase was greater in the cells treated with the combined treatment than in those treated with either 1,25(OH)2D3 or cisplatin alone. p21 and p27 expression was upregulated following co-treatment with both agents. The results of this study suggest that 1,25(OH)2D3 potentiates cisplatin-mediated cell growth inhibition and cell apoptosis, which involves the upregulation of Bax, a decrease in ERK and AKT phosphorylation levels, and increased p21 and p27 levels.
Preview · Article · Feb 2014 · International Journal of Molecular Medicine
[Show abstract][Hide abstract] ABSTRACT: Backgrounds/aims:
It has been previously demonstrated that vitamin D acts as a prognostic indicator of gastric cancer and may be correlated with the incidence risk of gastric cancer. However, the effect of 1,25-dihydroxyvitamin D3 on the apoptosis of human gastric cancer cells is unclear. The aim of this study was to determine whether 1,25-dihydroxyvitamin D3 induced the cellular apoptosis of BGC-823 gastric cancer cells and to determine the potential mechanism of action.
We demonstrate that 1,25-dihydroxyvitamin D3 induced the apoptosis of gastric cancer cells via the processing of PARP and cleavage of caspase 3. Additionally, an increase in BAX expression and a decrease in ERK1/2 and AKT phosphorylation were associated with 1,25-dihydroxyvitamin D3-induced apoptosis. The mRNA expression levels of VDR, CYP24A1, and p21 were increased significantly following 1,25-dihydroxyvitamin D3 treatment.
These findings suggest that 1,25-dihydroxyvitamin D3 exerts tumor-suppressive effects on BGC-823 human gastric cancer cells.
No preview · Article · Jan 2013 · Hepato-gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Background
Cardiomyocytes apoptosis is an important contributor to myocardial dysfunction and heart failure. Adiponectin has cardioprotective effects, potential mechanisms behind it are not clear in cardiomyocytes. The purpose of the study was to investigate whether adiponectin can block palmitate-induced apoptosis and the underlying biochemical mechanism in H9c2 cells.
H9c2 cells were treated with palmitate presence or absence of 2.5 μg/mL globular adiponectin. The effect on the cell viability of H9c2 cells was evaluated using MTT assay, and cell apoptosis was determined by Hoechst 33342 staining. Protein expression was measured using the western blot method.
Our results showed that the palmitate treatment induced apoptosis in H9c2 cells, which was associated with increasing the level of cleaved caspase-3 and cleaved PARP. Meanwhile, palmitate-induced apoptosis increased the protein level of p-ERK1/2, and decreased the protein level of p-Akt significantly. However, levels of both of these proteins were restored to the normal when pretreated with adiponectin, and followed with the decrease of cleaved caspase-3 and cleaved PARP. In line with these results, the protective effect of adiponectin can be blocked by PI3K/Akt inhibitor LY294002, and palmitate-induced apoptosis can be attenuated by ERK1/2 inhibitor U0126.
Taken together, the present study demonstrated that adiponectin protects H9c2 cells from palmitate-induced apoptosis via PI3K/Akt and ERK1/2 signaling pathways. Our results reveal a link between adiponectin and cardiomyocytes apoptosis, suggesting that adioponectin may be a promising therapeutic for the treatment of lipotoxicity cardiomyopathy.
Preview · Article · Oct 2012 · Lipids in Health and Disease
[Show abstract][Hide abstract] ABSTRACT: The association between a common variant of the ADIPOQ gene rs1501299 (+276G>T) and cardiovascular diseases (CVDs) outcomes has been reported with many studies. However, the evidence is insufficient for strong conclusions regarding CVDs and ADIPOQ rs15011299 (+276G>T). We performed a meta-analysis about the association between ADIPOQ rs1501299 (+276G>T) and CVDs risk using a predefined protocol, including 15 published studies with 5868 cases and 10,744 controls. The pooled data suggested a recessive protective effect of ADIPOQ rs1501299 (+276G>T) on CVDs for type 2 diabetes (T2D) population: the TT homozygote individuals had a reduced risk of developing CVDs compared to the carriers of G allele (OR=0.74, 95% confidence interval (CI): 0.58, 0.94; p=0.013). But there is still not enough evidence to indicate the association of the ADIPOQ rs1501299 (+276G>T) and the development of cardiovascular diseases (CVDs) outcomes in general population. In conclusion, our meta-analysis suggested that the ADIPOQ rs1501299 (+276G>T) polymorphism is a low-risk factor for the development of CVDs with T2D, but the association of this polymorphism with the susceptibility to CVDs in other populations remains unknown. It could be presumed that the ADIPOQ rs1501299 (+276G>T) be a potential cause of susceptibility to CVDs in persons with T2D, and it gives a new opportunity to investigate the mechanisms of CVDs susceptibility in T2D patients.
No preview · Article · Feb 2012 · Molecular and Cellular Endocrinology
[Show abstract][Hide abstract] ABSTRACT: Estrogens protect the vascular system in women, but its effect in men is unclear. We evaluated the impact of estrogen on the male cardiovascular system. Of 140 Chinese males, 55 (aged 61.2 ± 3.5) were cases and 60 (aged 59.5 ± 4.6) were controls. Compared with the control group, only serum estradiol ([E2]; P < .01) levels but not testosterone ([T]; P = .21) were significantly lower in the cases. Linear and multiple regression analysis showed that serum T was positively associated with triglycerides ([TG]; r = .439, P < .01) and d-dimer (r = .258, P < .05) but negatively associated with high-density lipoprotein cholesterol (HDL-C) levels (r = -.267, P < .05) and C-reactive protein (CRP; r = -.214, P < .05). Estradiol was highly associated with TG (r = .783, P < .01) and HDL-C (r = .515, P < .01) but was negatively related with low-density lipoprotein cholesterol (LDL-C; P < .05), total cholesterol/HDL-C (P < .05), CRP (P < .01), and d-dimer (P < .01). In conclusion, serum E2 and T levels affect coronary heart disease risk factors in males.