Induction of cancer-specific cytotoxicity towards human prostate and skin cells using quercetin and ultrasound

Bioflavonoids, such as quercetin, have recently emerged as a new class of chemotherapeutic drugs for the treatment of various cancer types, but are marred by their low potency and poor selectivity. We report that a short application of low-frequency ultrasound selectively sensitises prostate and skin cancer cells against quercetin. Pretreatment of cells with ultrasound (20 kHz, 2 W cm−2, 60 s) selectively induced cytotoxicity in skin and prostate cancer cells, while having minimal effect on corresponding normal cell lines. About 90% of the viable skin cancer cell population was lost within 48 h after ultrasound-quercetin (50 μM) treatment. Ultrasound reduced the LC50 of quercetin for skin cancer cells by almost 80-fold, while showing no effect on LC50 for nonmalignant skin cells

Pharmacodynamic and pharmacokinetic characterisation of RBx 7796: A novel 5-lipoxygenase inhibitor

Objective: RBx 7796, a 5-lipoxygenase inhibitor, was evaluated in in vivo efficacy models, in vitro ADME and in vivo pharmacokinetic models. Method: RBx 7796 was evaluated for inhibition of 5-lipoxygenase enzyme and release of LTB4 from isolated rat and human neutrophils. RBx 7796 was tested in allergic bronchoconstriction model in Balb/c mice and LPS induced airway hyperreactivity model in rats. RBx 7796 was evaluated for metabolic stability in liver microsomes and cytochrome P450 inhibition potential. Pharmacokinetic profile of RBx 7796 was also determined in rat and dog. Results: RBx 7796 inhibited 5-lipoxygenase enzyme and inhibited release of LTB4 from neutrophils. RBx 7796 also inhibited early and late airway reactivity following allergen challenge in mouse model. LPS induced increase in airway reactivity was blocked by RBx 7796. Compound was found to be stable in liver microsomes and devoid of major cytochrome P450 inhibition potential. The oral bioavailability of RBx 7796 in rat and dog was 83% and 47 %, respectively. Following repeated daily administration, compound did not exhibit any sign of accumulation and/or tendency to induce its own metabolism. Conclusion: The results suggest that RBx 7796 is an inhibitor of 5-lipoxygenase enzyme that is orally efficacious in two different models of airway reactivity. The molecule also demonstrated acceptable pharmacokinetic profile warranting further development. © 2008 Birkhaueser