New leukemia therapy study findings have been reported by investigators at Tohoku Pharmaceutical University, Cancer Research Institute

11-03-2006

Investigators publish new data in the report "Naringenin-induced apoptosis via activation of NF-kappaB and necrosis involving the loss of ATP in human promyeloleukemia HL-60 cells. Naringenin (NGEN), a flavonoid, has shown cytotoxicity in various human cancer cell lines and inhibitory effects on tumor growth. In this study, we investigated the apoptosis induced by NGEN via the activation of NF-kappaB and necrosis involving the loss of ATP in human promyeloleukemia HL-60 cells," scientists writing in the journal Toxicology Letters report.

"Exposure to NGEN induced apoptosis dose-dependently up until 0.5mM, but not at 1mM as demonstrated by a quantitative analysis of nuclear morphological change and flow cytometric analysis. An extensive inhibitor for caspases, abolished the NGEN-induced apoptosis. The apoptosis-triggering concentration of NGEN was shown to markedly promote the activation of caspase-3, and slightly promote that of caspase-9, but had no effect on caspase-8. NGEN-induced apoptosis caused by induction of specific NF-kappaB-binding activity and involving the degradation of IkappaBalpha. Incubation with a high concentration of NGEN (1mM) reduced intracellular ATP levels, but no change was observed at lower concentrations. NGEN increased dose-dependently hyperpolarization of mitochondrial membrane potential. This result indicates a common pathway to apoptosis and necrosis by NGEN. One of the mechanisms by NGEN-induced apoptosis may relate to the activation of NF-kappaB that correlates with degradation of IkappaBalpha," wrote S. Kanno and colleagues, Tohoku Pharmaceutical University, Cancer Research Institute.

The researchers concluded: "Induction of necrosis by NGEN suggests causing by intracellular ATP depletion and mitochondria dysfunctions."

Kanno and colleagues published their study in Toxicology Letters (Naringenin-induced apoptosis via activation of NF-kappaB and necrosis involving the loss of ATP in human promyeloleukemia HL-60 cells. Toxicology Letters, 2006;166(2):131-9).

Additional information can be obtained by contacting S. Kanno, Cancer Research Institute, Dept. of Pharmacology and Toxicology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.

The publisher of the journal Toxicology Letters can be contacted at: Elsevier Science Ireland Ltd., Customer Relations Manager, Bay 15, Shannon Industrial Estate, Co. Clare, Ireland.

Keywords: Japan, Sendai, Leukemia Therapy, Cancer Research, Hematology, Leukemia, Necrosis, Oncology, Toxicology, Tumors.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2006, Clinical Oncology Week via NewsRx.com.