ABSTRACT
Hesperetin, a Citrus bioflavonoid, exhibits anticancer, anti-inflammatory and antioxidant properties. However, its action and mechanism in inflammation-induced lung cancer is unknown. We have investigated anticancer effects of hesperetin in IL-1β-stimulated lung adenocarcinoma cell proliferation and COX-2 -mediated inflammation. The human lung adenocarcinoma A549 cells were serum-starved with or without HN (100 μM) for overnight and stimulated with IL-1β for varying durations. Cell viability and proliferation were assessed by MTT and wound healing assays. Cell cycle progression was measured by flow cytometry, and RT-PCR and immunoblotting methods were used to examine the expression COX-2 mRNA and protein, respectively. Protein stability assessed by cycloheximide chase assay. IL-1β caused a time- and dose-dependent increase in cell viability and proliferation, expression of COX-2 at transcription as well as translation levels, increased the stability of COX-2 protein, and PGE2 production while HN significantly decreased these changes. Further, IL-1β stimulated increased phosphorylation of ERK-1/2 and p65 subunit of NF-κB, which were reversed by HN in A549 cells. These results show that HN could inhibit IL-1β-stimulated cell proliferation, COX-2 expression and its regulation at translation level and PGE2 synthesis in A549 lung epithelial cells, indicating its anti-inflammatory and anticancer potential in lung cancer cells.
ABSTRACT
Sodium-orthovanadate (SOV) and seed powder of Trigonella foenum graecum Linn. (common name: fenugreek, family: Fabaceae) (TSP) besides being potential hypoglycemic agents have also been shown to ameliorate altered lipid metabolism during diabetes. This study evaluates the short-term effect of oral administration of SOV and TSP separately and in concert (for 21 days) on total lipid profile and lipogenic enzymes in tissues of alloxan diabetic rats. Diabetic rats showed 4-fold increase in blood glucose. The level of total lipids, triglycerides and total cholesterol in blood serum increased significantly during diabetes. During diabetes the level of total lipids increased significantly (P < 0.001) in liver and in kidney by 48% and 55%, respectively, compared to control. Triglycerides level increased by 32% (P < 0.01) in liver and by 51% (P < 0.005) in kidney, respectively, compared to control. Total cholesterol level also increased significantly in both liver and kidney (P < 0.01 and P < 0.001, respectively). The activities of NADP-linked enzymes; namely glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and the activities of lipogenic enzymes namely ATP-citrate lyase (ATP-CL) and fatty acid synthase (FAS) were decreased significantly in liver and increased in kidney during diabetes as compared to control. SOV and TSP administration to diabetic animals prevented the development of hyperglycemia and alteration in lipid profile in plasma and tissues and maintained it near normal. Maximum prevention was observed in the combined treatment with lower dose of SOV (0.2%) after 21 days. We are presenting for the first time effectiveness of combined treatment of SOV and TSP in amelioration of altered lipid metabolism during experimental type-I diabetes.
ABSTRACT
In order to evaluate the modulatory effects of manganese, high fat diet fed and alloxan diabetic rats were taken and the changes in the glucose oxidation, glycerol release and effects of manganese on these parameters were measured from adipose tissue. An insulin-mimetic effect of manganese was observed in the adipose tissue in the controls and an additive effect of insulin and manganese on glucose oxidation was seen when Mn2+ was added in vitro. The flux of glucose through the pentose phosphate pathway and glycolysis was significantly decreased in high fat fed animals. Although the in vitro addition of Mn2+ was additive with insulin when 14CO2 was measured from control animals, it was found neither in young diabetic animals (6-8 weeks old) nor in the old (16 weeks old). Both insulin and manganese caused an increased oxidation of carbon-1 of glucose and an increase of its incorporation into 14C-lipids in the young control animals; the additive effect of insulin and manganese suggests separate site of action. This effect was decreased in fat fed animals, diabetic animals and old animals. Manganese alone was found to decrease glycerol in both the control and diabetic adipose tissue in in vitro incubations. The results of the effects of glucose oxidation, lipogenesis, and glycerol release in adipose tissue of control and diabetic animals of different ages are presented together with the effect of manganese on adipose tissue from high fat milk diet fed animals.