RESUMEN
Fisetin, a natural flavonoid molecule, has been shown to have anticancer properties against various malignancies. In this investigation, we discovered that Fisetin decreased cell viability of both the treated skin cancer cell lines A375 and A431 in a dose and time-dependent manner. The IC50 values ranging from 57.60 µM ± 6.59 to 41.70 µM ± 1.25 in A375 and 48.70 µM ± 5.49 to 33.67 µM ± 1.03 for A431 at the observed time ranging between 24 h to 72 h of treatment remained quite enthusiastic when compared with the normal HEK 293 cells. Fisetin significantly decreased colony formation and migratory ability of the cancer cells. Flow cytometry analysis revealed that Fisetin significantly restricted the progression of skin cancer cells in the G0/G1 phase of the cell cycle and induced cells to undergo apoptosis by increasing reactive oxygen species, decreasing mitochondrial membrane potential, and elevating the count of early and late apoptotic cells. Our in silico studies of molecular docking followed by molecular dynamics simulation found that the interactions and stability of MTH1 protein with Fisetin further showed a considerable binding affinity for MTH1 (-11.4 kcal/mol) and developed stable complexes maintained throughout 100 ns trajectories. Our western blot analysis endorsed this. We found that Fisetin downregulated the expression levels of MTH1 also in addition, it played a crucial role in regulation of apoptotic events in cancer cells. We therefore, conclude that Fisetin anticancer properties against skin cancer cells are mediated through MTH1 inhibition followed by ATM and P53 upregulation.Communicated by Ramaswamy H. Sarma.
RESUMEN
The aim of present study is to investigate the role of 6-gingerol in ameliorating the renal injury in streptozotocin (STZ)-induced diabetic rats. The diabetes was induced by using a single dose of freshly prepared STZ (55 mg/kg body weight) intraperitoneally which causes the degeneration of pancreatic Langerhans islet ß-cells. The diabetic rats were treated with oral gavage of 6-gingerol (10 mg/kg b.w.). The treatment plan was continued for 8 weeks successively and the body weight and fasting blood glucose levels were weekly checked. The biochemical parameters like lipid profile, kidney profile, antioxidant enzyme levels, lipid peroxidation and anti-inflammatory marker levels were investigated after the treatment plant. The pathological condition of kidneys was examined by haematoxylin-eosin (H&E) staining besides this analysis of NF-κB protein expression by immuno-histochemistry was performed. Some of the major parameters in diabetes control vs. normal control were reported as fasting blood glucose (234 ± 10 vs. 102 ± 8 mg/dL), serum creatinine (109.7 ± 7.2 vs. 78.9 ± 4.5 µmol/L) and urea (39.9 ± 1.8 vs. 18.6 mg/dL), lipid profile levels were significantly enhanced in diabetic rats. Moreover, diabetic rats were marked with decreased antioxidant enzyme levels and increased inflammatory markers. Treatment with 6-gingerol significantly restored the fasting blood glucose level, hyperlipidaemia, Malondialdehyde (MDA) and inflammatory marker levels, NF-κB protein expression and augmented the antioxidant enzyme levels in the kidneys of diabetic rats. The kidney damage was significantly normalized by the treatment of 6-gingerol and it provides an evidence that this novel compound plays a significant role in the protection of kidney damage. These findings demonstrate that 6-gingerol reduces lipid parameters, inflammation and oxidative stress in diabetic rats, thereby inhibiting the renal damage. Our results demonstrate that use of 6-gingerol could be a novel therapeutic approach to prevent the kidney damage associated with the diabetes mellitus.
