Two novel cell culture models of buccal mucosal oral cancer from patients with no risk-habits of tobacco smoking or chewing.

Objective: Tobacco consumption is one of the major etiological factors for oral cancer, but it also develops in non-tobacco users, with unknown etiologies. Cellular models for tobacco associated oral cancer are available, however; reports of cellular models for studying non-tobacco associated oral cancer are limiting. We report here the establishment and characterization of two novel buccal mucosal cancer cell lines 'GBC02' and 'GBC035' derived from non-tobacco users.

Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state.

Background: Obesity is associated with increased risk, poor prognosis and outcome of therapy, in various cancers. Obesity-associated factors or adipokines, especially leptin and resistin, are purported to promote growth, survival, proliferation, and invasiveness of cancer cells. However, the mechanistic link between these adipokines and therapeutic response in malignancies is not clearly understood.

Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: role of adipokines.

Obesity, owing to adiposity, is associated with increased risk and development of various cancers, and linked to their rapid growth as well as progression. Although a few studies have attempted to understand the relationship between obesity and melanoma, the consequences of controlling body weight by reducing adiposity on cancer progression is not well understood. By employing animal models of obesity, we report that controlling obesity either by orlistat treatment or by restricting caloric intake significantly slows down melanoma progression.

Real time qualitative and quantitative GLUT4 translocation assay.

Insulin-stimulated glucose transporter 4 (GLUT4) translocation promoting glucose uptake is vital to glucose homeostasis and is a defined target of antidiabetic drug research. Existing functional assays to detect the process of GLUT4 translocation are hampered due to assay variability and low sensitivity, thus slowing down the progress towards the development of preferred alternative to insulin. This chapter describes a real time, visual, cell-based qualitative GLUT4 translocation assay suitable for screening insulin mimetics.

Diet-induced obesity increases melanoma progression: involvement of Cav-1 and FASN.

Recent population-based epidemiological studies strongly hint towards a link between obesity and its occurrence as well as progression of several cancers including melanoma. Although effects of obesity on breast, colon and liver cancers have been extensively investigated, the links between obesity and melanoma remain largely unexplored. Present study aimed to understand the effect of high fat diet-induced weight gain on susceptibility of C57BL/6J mice to melanoma.

Demonstration of a visual cell-based assay for screening glucose transporter 4 translocation modulators in real time.

Insulin-stimulated translocation of glucose transporter 4 (GLUT4) to cell membrane leading to glucose uptake is the rate-limiting step in diabetes. It is also a defined target of antidiabetic drug research. Existing GLUT4 translocation assays are based on time-consuming immunoassays and are hampered by assay variability and low sensitivity.

Cdk5 phosphorylates non-genotoxically overexpressed p53 following inhibition of PP2A to induce cell cycle arrest/apoptosis and inhibits tumor progression.

Background: p53 is the most studied tumor suppressor and its overexpression may or may not cause cell death depending upon the genetic background of the cells. p53 is degraded by human papillomavirus (HPV) E6 protein in cervical carcinoma. Several stress activated kinases are known to phosphorylate p53 and, among them cyclin dependent kinase 5 (Cdk5) is one of the kinase studied in neuronal cell system.

Hypolipidemic effect of fenugreek seeds is mediated through inhibition of fat accumulation and upregulation of LDL receptor.

Fenugreek (Trigonella foenum-graecum) seeds, used as a condiment, are documented for health benefits including amelioration of abnormalities in lipid homeostasis due to its hypolipidemic properties. However, molecular mechanisms underlying the hypolipidemic effect of fenugreek seeds remain obscure. In this study, hypolipidemic effect of a novel thermostable extract of fenugreek seeds (TEFS) was evaluated in vitro by employing differentiating and differentiated 3T3-L1 cells, and HepG2 cells cultured in normal or sterol-enriched conditions.

Hypoglycemic effect of a novel dialysed fenugreek seeds extract is sustainable and is mediated, in part, by the activation of hepatic enzymes.

A novel preparation of a dialysed aqueous extract of fenugreek seeds (FSE) that stimulates the insulin signalling pathway was reported previously (Vijayakumar et al., 2005). The present study was designed to investigate the long-term effects (multiple dose effect) of this FSE preparation on the blood glucose level and body weight, and a short-term effect (single dose effect) on serum insulin and hepatic enzymes, in experimentally induced diabetic conditions.

Methyl-beta-cyclodextrin enhances the susceptibility of human breast cancer cells to carboplatin and 5-fluorouracil: involvement of Akt, NF-kappaB and Bcl-2.

The response rates of extensively used chemotherapeutic drugs, carboplatin (Carb) or 5-fluorouracil (5-FU) are relatively disappointing because of considerable side effects associated with their high-dose regimen. In the present study, we determined whether treatment with a cholesterol depleting agent, methyl-beta-cyclodextrin (MCD), enhances the weak efficacy of low doses of Carb or 5-FU in human breast cancer cells. Data demonstrate that pretreatment with MCD significantly potentiates the cytotoxic activity of Carb and 5-FU in both MCF-7 and MDA-MB-231.

DNA damaging drugs-induced down-regulation of Bcl-2 is essential for induction of apoptosis in high-risk HPV-positive HEp-2 and KB cells.

DNA damaging chemotherapeutic agents like carboplatin (Carb) and 5-fluorouracil (5-FU), whose effects are mediated through diverse intracellular targets, induce apoptosis in various cancer cells including human papillomavirus (HPV) positive HEp-2 and KB cells. The present work reports the involvement of Bcl-2 in response to the exposure of HEp-2 and KB cells to Carb or 5-FU. We demonstrate that both these drugs are potent inducers of apoptosis.

The hypoglycaemic activity of fenugreek seed extract is mediated through the stimulation of an insulin signalling pathway.

The in vivo hypoglycaemic activity of a dialysed fenugreek seed extract (FSE) was studied in alloxan (AXN)-induced diabetic mice and found to be comparable to that of insulin (1.5 U kg(-1)). FSE also improved intraperitoneal glucose tolerance in normal mice.

Doxycycline potentiates antitumor effect of cyclophosphamide in mice.

Cyclophosphamide (CPA) is a widely used chemotherapeutic drug in neoplasias. It is a DNA and protein alkylating agent that has a broad spectrum of activity against variety of neoplasms including breast cancer. The therapeutic effectiveness of CPA is limited by the high-dose hematopoietic, renal, and cardiac toxicity that accompanies the systemic distribution of liver-derived activated drug metabolites.