Induction of apoptosis by furanodiene in HL60 leukemia cells through activation of TNFR1 signaling pathway.
Furanodiene, a natural product isolated from Curcuma wenyujin, has been reported to produce cytotoxic effect. In this study, we investigated its effects on human leukemia HL60 cells. Furanodiene induced apoptosis of HL60 cells, characterized by DNA fragmentation, cleavage of poly (ADP-ribose) polymerase (PARP), caspase-3, caspase-8 and caspase-9. In the Bcl-2 family proteins, Bid protein (a substrate of caspase-8) was activated by furanodiene, but Bcl-2, Bax and Bcl-xL proteins were not influenced by furanodiene stimulation. Moreover, furanodiene treatment caused the upregulation of tumor necrosis factor receptor 1 (TNFR1), the formation of TNFR1 complex and an obvious production of TNF-alpha in HL60 cells. The soluble TNFR1 receptor effectively inhibited furanodiene-induced apoptosis. Taken together, furanodiene could inhibit the growth of leukemia cells via induction of apoptosis, and TNFR1-mediated extrinsic apoptotic pathways explains furanodiene-induced apoptosis.
Ma
Enlong
E
Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, PR China. maenlong@hotmail.com
Wang
Xiaolong
X
Li
Yanchun
Y
Sun
Xiuyan
X
Tai
Wenjiao
W
Li
Te
T
Guo
Tao
T
D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D017931:DNA Primers; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D005663:Furans / Q000494:pharmacology*; D018922:HL-60 Cells; D006574:Heterocyclic Compounds, 2-Ring / Q000494:pharmacology*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
D017931:DNA Primers; D005663:Furans; D006574:Heterocyclic Compounds, 2-Ring; D019253:Proto-Oncogene Proteins c-bcl-2; D047888:Receptors, Tumor Necrosis Factor, Type I; C442489:furanodiene; D045304:Cytochromes c; D020169:Caspases