Diacetyl Hexamethylene Diamine (CAHB) Exerts Pro-Apoptotic and Anti-Proliferative Function in Leukemic T Lymphocytes via Downregulating PI3K/Akt Signaling
Ye Hong, Jia Zhang, Qunyi Guo, Min Zhu, Baoguo Chen, Wenda Luo
Department of Hematology and Oncology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou, Zhejiang, China (mainland)
Med Sci Monit 2019; 25:5211-5218
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: Cell Proliferation, Diacetyl, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Proto-Oncogene Proteins c-akt