C-glycosyl flavone from Urginea indica inhibits proliferation & angiogenesis & induces apoptosis via cyclin-dependent kinase 6 in human breast, hepatic & colon cancer cell lines.

BACKGROUND & OBJECTIVES: Search for novel compounds beneficial to the treatment of cancer attracts a great deal of attention. We earlier demonstrated the isolation of 5,7-dihydroxy-2-[4'-hydroxy-3'-(methoxymethyl)phenyl]-6-C-ß-glucopyranosyl flavone, a novel C-glycosyl flavone from Urginea indica bulb. The present study was undertaken to investigate the effect of this novel compound on human normal epithelial and breast, hepatic and colon cancer cell lines. METHODS: : The maximum non-toxic concentration (MNTC) and cytotoxicity of C-glycosyl flavone were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell cycle was analyzed by flow cytometry. Docking studies were performed to predict possible targets. Levels of cyclin-dependent kinase 1 (CDK1) and CDK6, Bcl2 and BAX and cytochrome c were quantified by specific ELISA. Mitochondrial membrane potential was determined using JC-1 dye. Apoptosis was quantified by Annexin V ELISA method. RESULTS: : Flow cytometry analysis demonstrated G0/G1 arrest. In silico docking studies predicted CDK1 and CDK6 as a possible target of C-glycosyl flavone. In vitro study confirmed CDK6 as the main target in C-glycosyl flavone-treated cancer cell lines. C-glycosyl flavone treatment also induced membrane blebbing, chromatin fragmentation and nucleosome formation. C-glycosyl flavone treatment caused marked loss of mitochondrial membrane potential, decrease in Bcl2/BAX ratio and activation of caspase-3 and release of caspase-9 and cytochrome c. In addition, C-glycosyl flavone inhibited the tumour-induced angiogenesis and reduced the vascular endothelial growth factor levels. Similarly, CDK6 inhibitor significantly inhibited proliferation and angiogenesis and induced apoptosis in tested cell lines. INTERPRETATION & CONCLUSIONS: The results indicate that C-glycosyl flavone may exert induction of apoptosis, cell cycle arrest and inhibition of angiogenesis via CDK6. Thus, targeting CDK6 using C-glycosyl flavone may serve as a novel therapeutic approach for the treatment of breast, hepatic and colon cancers.

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.

Clinical study to know the efficacy of Amlexanox 5% with other topical Antiseptic, Analgesic and Anesthetic agents in treating minor RAS.

BACKGROUND: To evaluate the efficacy of topical antiinflammatory agent (amlexanox 5%), along with topical antiseptic, analgesic, and anesthetic agent (benzalkonium chloride 0.01%, choline salicylate 8.7% and lidocaine hydrochloride 2%), in promoting ulcer healing, decreasing ulcer size, erythema, pain and recurrence in minor RAS. MATERIALS & METHODS: A randomized control trial was conducted on 100 patients of RAS who fulfilled the inclusion criteria. The number, size, erythema and pain with the ulcer were recorded. Visual analogue scale (VAS) and erythema scale were used to record pain and erythema. 50 patients comprising the study group received anti inflammatory paste (amlexanox 5%) applied four times daily and the control group of 50 patients received topical antiseptic, analgesic, and anesthetic agent (benzalkonium chloride 0.01%, choline salicylate 8.7% and lidocaine hydrochloride 2%) paste, patients were evaluated after 3rd, 6th, 9th and on 30th, 60th day for recurrence. RESULTS: The study group had reduction in ulcer number, size; erythema, pain and frequency of ulcers during follow up. The healing period and recurrence of ulceration reduced in both the groups but the study group had significant reduction in 30th and 60th day follow up for recurrence of ulcers. CONCLUSION: Amlexanox 5% can reduce the frequency, duration and symptoms associated with the aphthous ulcers with no sideeffects attributed to the drug. How to cite the article: Darshan DD, Kumar CN, Kumar AD, Manikantan NS, Balakrishnan D, Uthkal MP. Clinical study to know the efficacy of Amlexanox 5% with other topical Antiseptic, Analgesic and Anesthetic agents in treating minor RAS. J Int Oral Health 2014;6(1);5-11.

Sound waves for unsound entities: an electronic search study to evaluate the diagnostic efficacy of ultrasonography in cysts and tumors of maxillofacial region.

OBJECTIVE: The purpose of this electronic search study was to evaluate the diagnostic efficacy of ultrasonography in cysts and tumors of maxillofacial region. MATERIALS AND METHODS: An electronic search was performed for articles published from January 1989 to august 2009. RESULTS: Only 30 publications were searched and 22 publications showed high level of evidence (4 review articles, 12 clinical studies, 2 case reports, 1 quantitative analysis, 2 research articles and 1 preliminary report) with total of more than 2000 patients. CONCLUSION: Ultrasonography is a noninvasive, low cost procedure, and recommended as a complimentary imaging modality.

Antipyrine kinetics in undernourished diabetics.

In developing countries diabetics frequently suffer from varying grades of malnutrition. The combined effect of malnutrition and non-insulin dependent diabetes (NIDDM) on the drug metabolising enzyme system has been evaluated using antipyrine as a protodrug. All the patients were under treatment and their plasma glucose values were within normal limits. The AUC of antipyrine was similar in all the groups. Although none of the kinetic parameters was altered in normal diabetics, the clearance of antipyrine was decreased and its half life was prolonged, with an increase in volume of distribution, in undernourished diabetics compared to undernourished controls. The results indicate that diabetes per se may not influence antipyrine kinetics when the blood glucose is well under control, but in the presence of undernutrition, it significantly alters the disposition of the drug.