Molecular mechanisms of anti-tumor properties of P276-00 in head and neck squamous cell carcinoma.

Background: Tumors of the head and neck present aggressive pathological behavior in patients due to high expression of CDK/CCND1 proteins. P276-00, a novel CDK inhibitor currently being tested in clinic, inhibits growth of several cancers in vitro and in vivo. The pre clinical activity of P276-00 in head and neck cancer and its potential mechanisms of action at molecular level are the focus of the current studies.

NF-κB dependent anti-inflammatory activity of chlorojanerin isolated from Saussurea heteromalla.

Medicinal plants have shown great promise as a source of novel drug compounds for the treatment of inflammatory disorders. In our search for new entities with anti-inflammatory potential, the extracts of the whole plant of Saussurea heteromalla (family-Asteraceae), collected from Himalayas, were evaluated in the high throughput screen for TNF-α and IL-6 inhibitors. The extract blocked TNF-α and IL-6 production in LPS stimulated THP-1 cells (human acute monocyte leukemia cell line) completely at 10 and 30 μg/ml.

NF-κB-mediated anti-inflammatory activity of the sesquiterpene lactone 7-hydroxyfrullanolide.

Microarray technology can be used to study the molecular mechanisms of new chemical entities with the aim to develop effective therapeutics. 7-Hydroxyfrullanolide (7HF) is a sesquiterpene lactone that was found to be efficacious in multiple animal models of inflammation by suppression of pro-inflammatory cytokines; however, its molecular mechanism of action remains unclear. We investigated the effects of 7HF on lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells using microarray-based gene expression studies and explored the molecular targets affected.

Phenotypic and genotypic assessment of concomitant drug-induced toxic effects in liver, kidney and blood.

Several studies have characterized drug-induced toxicity in liver and kidney. However, the majority of these studies have been performed with 'individual' organs in isolation. Separately, little is known about the role of whole blood as a surrogate tissue in drug-induced toxicity.

7-hydroxyfrullanolide, a sesquiterpene lactone, inhibits pro-inflammatory cytokine production from immune cells and is orally efficacious in animal models of inflammation.

A promising therapeutic approach to reduce pathological inflammation is to inhibit the increased production of pro-inflammatory cytokines (e.g., TNF-alpha, IL-6).