Homoharringtonine induces apoptosis of endothelium and down-regulates VEGF expression of K562 cells.
Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evidence suggests that angiogenesis may play an important role in hematological malignancies, such as leukemia. However, whether HHT can relieve leukemia by anti-angiogenesis is still unknown. We investigated the anti-angiogenesis potential of HHT with the human umbilical vein endothelial cell line (ECV304) and leukemic cell line (K562) in vitro. Cellular proliferation was determined by MTT assay and apoptosis was analyzed by flow cytometry. The mRNA expression of vascular endothelial growth factor (VEGF) was assessed by RT-PCR and VEGF protein production was detected by Western blot. Inhibition of cell proliferation and induction of apoptosis by HHT were discovered in ECV304 cells, and appeared in a dose- and time-dependent manner. Also, treatment with HHT caused down-regulation of VEGF mRNA expression in K562 cells in similar dose- and time-dependent manner and inhibition of VEGF protein production in K562 cells in response to the enhancing concentration of HHT. The results demonstrated that HHT could also induce apoptosis in endothelium and down-regulate VEGF expression in K562 cells. In conclusion, we believe HHT has anti-angiogenesis potential and speculate that HHT might exert its anti-leukemia effects via reduction of angiogenesis.
Ye
Xiu-jin
XJ
Department of Hematology, the First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003, China.
Lin
Mao-fang
MF
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D006248:Harringtonines / Q000494:pharmacology*; D000077863:Homoharringtonine; D006801:Humans; D020014:K562 Cells; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D014471:Umbilical Veins / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D006248:Harringtonines; D042461:Vascular Endothelial Growth Factor A; D000077863:Homoharringtonine