Abstract

BACKGROUND: T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy caused by abnormal proliferation of immature T cell progenitors. Chemotherapy of T-ALL usually consists of induction, consolidation, and long-term maintenance. Diacetyl hexamethylene diamine (CAHB) is a newly developed agent that induces the differentiation of malignant cells and deprives their clonal growth ability. Since its effect on T-ALL has not been previously determined, we evaluated its potential function in the Jurkat cell line.

MATERIAL AND METHODS: MTT assay was conducted to evaluate the cytotoxicity and anti-proliferative effect of CAHB. The apoptosis level of CAHB-treated Jurkat cells was evaluated using flow cytometry via staining with Annexin V/PI or cleaved-caspase-3. The alteration of mitochondrial membrane potential was determined by flow cytometry. The expression of Bax and Bcl-2 was evaluated by RT-PCR and Western blot. Western blot was also used to assess the activation of Akt.

RESULTS: CAHB inhibited the proliferation and promoted the apoptosis of Jurkat cells in a time- and dose-dependent manner by decreasing activation of Akt, reducing the mitochondrial membrane potential, and downregulating the Bcl-2/Bax ratio.

CONCLUSIONS: Our data suggest that CAHB might be regarded as a novel treatment agent for T-ALL since it can induce apoptosis and inhibit proliferation of the T-ALL cell line at a relatively low level.

Keywords: Diacetyl, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Proto-Oncogene Proteins c-akt, Antineoplastic Agents, Phytogenic, Apoptosis, Cell Survival, Diamines, Down-Regulation, Jurkat Cells, Membrane Potential, Mitochondrial, Phosphatidylinositol 3-Kinases, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Proto-Oncogene Proteins c-bcl-2