Pure Total Flavonoids from Citrus paradisi Macfad InduceLeukemia Cell Apoptosis In Vitro

Objective： To investigate the potential effect of pure total flavonoids from Citrus paradisi Macfad peel（PTFC） on the proliferation and apoptosis of human myeloid leukemia cells Kasumi-1, HL-60 and K562, and the underlying mechanisms. Methods： PTFC was extracted from Citrus paradisi Macfad peel and was identified by high performance liquid chromatography. The effect of PTFC on the proliferation and apoptosis of leukemia cells were determined by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide, fluorescent microscopy and flow cytometry, respectively. The effect of PTFC on the expression levels of apoptosis-related regulators was determined by Western blot assay. Results： Treatment with PTFC inhibited leukemia cell proliferation in a dose-and time-dependent manner and triggered Kasumi-1 cell apoptosis. Treatment with PTFC significantly increased the levels of activated poly adenosine diphosphate-ribosepolymerase and caspase-3/-9, but reduced the levels of Mcl-1 expression in Kasumi-1 cells. However, PTFC did not obviously induce HL-60 cell apoptosis. Conclusion： PTFC inhibited leukemia cell proliferation and induced their apoptosis by modulating apoptosisrelated regulator expression in leukemia cells in vitro.

New insight into the oncogenic mechanism of the retroviral oncoprotein Tax

Human T cell leukemia virus type 1(HTLV-1),an etio-logical factor that causes adult T cell leukemia and lym-phoma(ATL),infects over 20 million people worldwide.About 1 million of HTLV-1-infected patients develop ATL,a highly aggressive non-Hodgkin's lymphoma without an effective therapy.The pX region of the HTLV-1 viral genome encodes an oncogenic protein,Tax,which plays a central role in transforming CD4+ T lymphocytes by deregulating oncogenic signaling pathways and promoting cell cycle progression.Expression of Tax following viral entry is critical for promoting survival and proliferation of human T cells and is required for initiation of oncogenesis.Tax exhibits diverse functions in host cells,and this oncoprotein primarily targets IκB kinase complex in the cytoplasm,resulting in persistent activation of NF-κB and upregulation of its responsive gene expressions that are crucial for T cell survival and cell cycle progression.We here review recent advances for the pathological roles of Tax in modulating IκB kinase activity.We also discuss our recent observation that Tax connects the IκB kinase complex to autophagy pathways.Understanding Tax-mediated pathogenesis will provide insights into development of new therapeutics in controlling HTLV-1-associated diseases.