Researchers at Zhejiang University, Institute of Pharmacology and Toxicology have published new data on leukemia cell biology

03-01-2007

Researchers detail in "MZ3 induces apoptosis in human leukemia cells," new data in leukemia. "4-(4-Bromophenyl)-2,3-dihydro-N,3-bis(3,4,5-trimethoxyphenyl)-2-oxoidmi-dazole-1-carboxamide (MZ3) is one of the synthesized combretastatin-A-4 analogues and has been reported that it displayed a promising specific activity against leukemia cell lines. Our purpose was to investigate the mechanism of MZ3's cytotoxicity," scientists in People's Republic of China report.

"Cytotoxicity was measured by MTT method, apoptosis was measured by flow cytometry. DNA fragmentation was tested by agarose gel electrophoresis. Mitochondrial membrane potential (DeltaPsim) was detected by JC1 staining and flow cytometry, while intracellular reactive oxygen species (ROS) was detected by 5-(and-6)-carboxy-2'-7'-dichlorofluorescin diacetate staining and flow cytometry. Protein expression was analyzed by western blotting. In vivo activity of MZ3 was assayed through severe combined immunodeficiency (SCID) mice model of human leukemia engrafts. MZ3 exhibited high anti-cancer activity in six leukemia cell lines, including two drug-resistant cell lines. MZ3 induced DNA fragmentation, and caused an elevation of ROS and a loss of DeltaPsim in HL60 cells. MZ3 also induced the activation of caspase-3, influenced the expression of Bcl-2 family members, MAPKs and other proteins relative to mitochondria-induced apoptosis. In addition, N-acetylcysteine cannot inhibit HL60 cell apoptosis caused by MZ3. Furthermore, a prolonged survival time was observed after treatment with MZ3 in SCID mice model of human leukemia engrafts," wrote L. Fang and colleagues, Zhejiang University, Institute of Pharmacology and Toxicology.

The researchers concluded: "MZ3 is a potent compound against leukemia cell lines both in vitro and in vivo, and the mitochondrial pathway mediated by Bcl-2 protein family and MAPKs might be involved in signaling MZ3-induced apoptosis."

Fang and colleagues published their study in Cancer Chemotherapy and Pharmacology (MZ3 induces apoptosis in human leukemia cells. Cancer Chemotherapy and Pharmacology, 2007;59(3):397-405).

For additional information, contact L. Fang, Institute of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Zhejiang University, 353# Yan'an Rd., Hangzhou, Zhejiang, 310031, China.

The publisher's contact information for the journal Cancer Chemotherapy and Pharmacology is: Springer, 233 Spring Street, New York, NY 10013, USA.

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.