C-glycosyl Flavone from Urginea indica Inhibits Growth and Dissemination of Ehrlich Ascites Carcinoma Cells in Mice.

BACKGROUND: C-glycosyl flavone, a phytochemical constituent in U.indica bulb, has been reported to possess cytotoxic activity. OBJECTIVE: The present study aims to investigate the toxicity and anticancer potentials of C-glycosyl flavone against Ehrlich ascites carcinoma mice model. METHOD: In present study, acute and chronic toxicity along with antitumor activity of C-glycosyl flavone isolated from U.indica bulb were Performed using in vitro and in vivo methods. Acute and chronic toxicity of C-glycosyl flavone was evaluated using Swiss albino mice. The effect of C-glycosyl flavone on proliferation of Ehrlich ascites carcinoma (EAC) cells was determined. Further, growth inhibition and dissemination were studied using EAC induced mice model. RESULTS: C-glycosyl flavone showed significant therapeutic potency against EAC cells in terms of reduced viability, cell cycle arrest, induction of apoptosis, inhibition of capillary formation, reduced VEGF levels. Moreover, there was reduction in body weight, tumor volume, viable tumor cells, increased survival of EAC induced mice upon C-glycosyl flavone treatment. Treatment also reduced dissemination of EAC cells into heart, kidney, liver and brain and diminished the pathological alterations induced by EAC cells in mice. In addition, there was an improvement in hemoglobin levels and counts of RBC, neutrophils, lymphocytes and monocytes in C-glycosyl flavone-treated mice with tumor. An enhancement of antioxidant status in C-glycosyl flavone treated EAC-bearing mice which appeared in terms of decreased serum thiobarbituric acid reactive substance and lipid peroxidation, increased GSH, SOD, Catalase and GPX. These results were comparable to a standard 5- fluorouracil treatment. C-glycosyl flavone exhibited safety profile in toxicity studies. CONCLUSION: Our study confirms the therapeutic potency of C-glycosyl flavone against EAC in inhibition of dissemination and growth of EAC in mice.

Protective effect of 3-O-methyl quercetin and kaempferol from Semecarpus anacardium against H2O2 induced cytotoxicity in lung and liver cells.

BACKGROUND: Hydrogen peroxide is continuously generated in living cells through metabolic pathways and serves as a source of reactive oxygen species. Beyond the threshold level, it damages cells and causes several human disorders, including cancer. METHODS: Effect of isolated 3-O-methyl quercetin and kaempferol on H2O2 induced cytotoxicity, ROS formation, plasma membrane damage, loss of mitochondrial membrane potential, DNA damage was evaluated in normal liver and lung cells. The RT-PCR analysis used to determine Nrf 2 gene expression. Calorimetric ELISA was used to determine Nrf2 and p-38 levels. Expression of SOD and catalase was analyzed by Western blot analysis. RESULTS: The present study isolated 3-O-methyl quercetin and kaempferol from the stem bark. They protected normal lung and liver cells from H2O2 induced cytotoxicity, ROS formation, membrane damage and DNA damage. Pre-treatment with 3-O-methyl quercetin and kaempferol caused translocation of Nrf2 from cytosol to nucleus. It also increased expression of p-p38, Nrf2, SOD and catalase in H2O2 treated lung and liver cells. CONCLUSION: The flavonoids isolated from S. anacardium significantly reduced H2O2 induced stress and increased expression of Nrf2, catalase and superoxide dismutase-2 indicating cytoprotective nature of 3-O-methylquercetin and kaempferol.