CLC number: TP391
On-line Access:
Received: 2003-02-21
Revision Accepted: 2003-09-06
Crosschecked: 0000-00-00
Cited: 10
Clicked: 6561
YE Xiu-jin, LIN Mao-fang. Homoharringtonine induces apoptosis of endothelium and down-regulates VEGF expression of K562 cells[J]. Journal of Zhejiang University Science A, 2004, 5(2): 230-234.
@article{title="Homoharringtonine induces apoptosis of endothelium and down-regulates VEGF expression of K562 cells",
author="YE Xiu-jin, LIN Mao-fang",
journal="Journal of Zhejiang University Science A",
volume="5",
number="2",
pages="230-234",
year="2004",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.2004.0230"
}
%0 Journal Article
%T Homoharringtonine induces apoptosis of endothelium and down-regulates VEGF expression of K562 cells
%A YE Xiu-jin
%A LIN Mao-fang
%J Journal of Zhejiang University SCIENCE A
%V 5
%N 2
%P 230-234
%@ 1869-1951
%D 2004
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.2004.0230
TY - JOUR
T1 - Homoharringtonine induces apoptosis of endothelium and down-regulates VEGF expression of K562 cells
A1 - YE Xiu-jin
A1 - LIN Mao-fang
J0 - Journal of Zhejiang University Science A
VL - 5
IS - 2
SP - 230
EP - 234
%@ 1869-1951
Y1 - 2004
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.2004.0230
Abstract: 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.
[1] Bellamy, W.T., Richter, L., Frutiger, Y., Grogan, T.M., 1999.Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies.Cancer Res,59(3):728-733.
[2] Browder, T., Butterfield, C.E., Krling, B.M., Shi, B., Marshall, B., O'Reilly, M.S., Folkman, J., 2000. Anti-angiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer.Cancer Res,60(4):1878-1886.
[3] Cai,Z., Lin, M., Wuchter, C., Ruppert, V., Drken, B., Ludwig, W.D., Karawajew, L., 2001. Apoptotic response to homoharringtonine in human wt p53 leukemic cells is independent of reactive oxygen species geneation and implicates Bax translocation, mitochondrial cytochrome c release and caspase activation.Leukemia,15(4):567-574.
[4] Feldman, E., Arlin, Z., Ahmed, T., Mittelman, A., Puccio, C., Chun, H., Cook, P., Baskind, P., 1992. Homo-harringtonine is safe and effective for patients with acute myelogenous leukemia.Leukemia,6(11):1185-1188.
[5] Fiedler, B.W., Graeven, U., Ergn, S., Verago, S., Kilic, N., Stockschlder, M. K., Hossfeld, D., 1997. Vascular endothelial growth factor, a possible paracrine growth factor in human acute myeloid leukemia.Blood,89(6):1870-1875.
[6] O'Brien, S., Kantarjian, H., Keating, M., Meran, M., Koller, C., Robertson, E., Hester, J., Rios, M.B., Andreeff, M. , Talpaz, M., 1995. Homoharringtonine therapy induces responses in patients with chronic myelogenous leukemia in late chronic phase.Blood,86(9):3322-3326.
[7] O'Brien, S., Kantarjian, H., Koller, C., Feldman, E., Beran, M., Andreeff, M., Giralt, S., Cheson, B., Keating, M., Freireich, E., Rios, M.B., Talpaz, M., 1999. Sequential homoharringtonine and interferon-alpha in the treatment of early chronic phase chronic myelogenous leukemia.Blood,93(12):4149-4153.
[8] Padro, T., Ruiz, S., Bieker, R., Brger, H., Steins, M., Kienast, J., Berdel, W.E., Mesters, R.M., 2000. Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia.Blood,95(8):2637-2644.
[9] Perez-Atayde, A.R., Sallan, S.E., Tedrow, U., Connors, S., Allred, E., Folkman, J., 1997. Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia.Am J Pathol,150(3):815-821.
[10] Roboz, G.J., Dias, S., Lam, G., Soignet, S.L., Warrell Jr, R.P., Rafii, S., 2000. Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis.Blood,96(4):1525-1530.
[11] Tujebajeva, R.M., Graifer, D.M., Karpova, G.G., Ajtkhozhina, N.A., 1989. Alkaloid homoharringtonine inhibits polypeptide chain elongation on human ribosomes on the step of peptide bond formation.FEBS Lett,257(2):254-256.
[12] Vacca, A., Iurlaro, M., Ribatti, D., Minischetti, M., Nico, B., Ria, R., Pellegrino, A., Dammacco, F., 1999. Antiangiogenesis is produced by nontoxic doses of vinblastine.Blood,94(12):4143-4155.
[13] Zhou, D.C., Zittoun, R., Marie, J.P., 1995. Homorringtonine: an effective new natural product in cancer chemotherapy.Bull Cancer,82:987-995.
Open peer comments: Debate/Discuss/Question/Opinion
<1>
Luis@UNESP-Brazil<regasini@hotmail.com>
2012-01-13 19:24:21
Important manuscript to Natural Products Chemistry and Pharmacology.