RESUMO
Angiogenin (ANG), a multifunctional protein known to induce blood vessel formation, is a potential biomarker for cardiovascular diseases; however, whether it is affected by vitamin D supplementation is not known. This interventional study in vitamin D-deficient Saudi adults was designed to investigate it. A total of 100 vitamin D-deficient Saudi adults aged 30-50 years were randomly selected to undergo 6-month vitamin D supplementation. Circulating levels of fasting glucose, lipids, vitamin D, apolipoproteins (AI, AII, B, CI, CII, CIII, E, and H), and ANG were measured using commercially available assays at baseline and after six months. Overall, vitamin D levels increased significantly post intervention. With this, levels of apo-CIII and apo-E significantly increased (p-values of 0.001 and 0.009, respectively) with a significant parallel decrease in apo-B (p = 0.003). ANG levels were significantly positively associated with most apolipoproteins and inversely correlated with HDL-cholesterol. Post intervention, the changes in ANG levels were positively correlated with apo-E (r = 0.32; p < 0.01 in all subjects and r = 0.40; p < 0.05 in males). Vitamin D supplementation may modestly affect ANG levels. The association observed between ANG and apo-E is worthy of further investigation since both biomarkers have been linked to neurodegenerative disorders.
RESUMO
PURPOSE: Cisplatin resistance is a major concern in ovarian cancer treatment. The aim of this study was to investigate if wedelolactone could perform better in resistant ovarian cancer cells when used in combination with cisplatin. METHODS: Growth inhibitory potential of wedelolactone and cisplatin was investigated through MTT reduction assay in ovarian cancer cell lines including A2780 (sensitive), A2780cisR (cisplatin resistant) and A2780ZD0473R. Resistance factor (RF) of drugs was determined in these three cell lines. Combination index (CI) was calculated as a measure of combined drug action. Effect of this combination on changes in the cellular accumulation of platinum levels and platinum-DNA binding was also determined in vitro using AutoDock Vina while the effect of wedelolactone on inhibition of possible key culprits of resistance including Chk1, CD73, AT tip60, Nrf2, Brd1, PCAF, IGF1, mTOR1 and HIF2α was investigated in silico. RESULTS: Cisplatin and wedelolactone showed a dose-dependent growth inhibitory effect. RF value of wedelolactone was 1.1 in the case of A2780cisR showing its potential to bring more cell death in cisplatin-resistant cells. CI values were found to vary showing antagonistic to additive outcomes. Additive effect was observed for all sequences of administration (0/0, 0/4 and 4/0 h) in A2780cisR. Enhanced cellular accumulation of cisplatin was observed in parent and resistant cells on combination. Docking results revealed that among the selected oncotargets, Chk1, CD73, Nrf2, PCAF and AT tip60 were more vulnerable to wedelolactone than their respective standard inhibitors. CONCLUSION: These findings have shown that additive outcome of drug combination in A2780cisR and raised levels of platinum accumulation followed a clear pattern. This observation indicates that the presence of wedelolactone might have contributed to sensitize A2780cisR. However, in silico results point to the possible effects of this compound on epigenetic factors involving tumor microenvironment, epithelial mesenchymal transition, and immune-checkpoint kinases.
