Diacetyl Hexamethylene Diamine (CAHB) Exerts Pro-Apoptotic and Anti-Proliferative Function in Leukemic T Lymphocytes via Downregulating PI3K/Akt Signaling

• Published in: Medical science monitor Vol. 25; pp. 5211 - 5218
• Main Authors: Hong, Ye, Zhang, Jia, Guo, Qunyi, Zhu, Min, Chen, Baoguo, Luo, Wenda
• Format: Journal Article
• Language: English
• Published: United States International Scientific Literature, Inc 13.07.2019
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Diacetyl; Diamines - metabolism; Diamines - pharmacology; Down-Regulation - drug effects; Humans; Jurkat Cells; Lab/In Vitro Research; Membrane Potential, Mitochondrial - drug effects; Phosphatidylinositol 3-Kinases - metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Signal Transduction - drug effects
• ISSN: 1643-3750; 1234-1010; 1643-3750
• DOI: 10.12659/MSM.915840

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.