APOPTOSIS INDUCED BY DNA TOPOISOMERASE-I AND TOPOISOMERASE-II INHIBITORS IN HUMAN LEUKEMIC HL-60 CELLS

被引：90

作者：

SOLARY, E ^{[1
]}

BERTRAND, R ^{[1
]}

POMMIER, Y ^{[1
]}

机构：

[1] UNIV MED,ONCOHEMATOL LAB,DIJON,FRANCE

来源：

LEUKEMIA & LYMPHOMA | 1994年 / 15卷 / 1-2期

关键词：

HL-60; CELLS; APOPTOSIS; DNA TOPOISOMERASE INHIBITORS; ETOPOSIDE (VP-16); ADRIAMYCIN; CAMPTOTHECIN; LEUKEMIA; DNA DAMAGE; CELL CYCLE;

D O I：

10.3109/10428199409051674

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The induction of apoptosis following topoisomerase inhibitors proceeds in at least three distinct steps: (1) induction of cleavable complexes (potentially lethal damage), (2) topoisomerase-induced DNA damage, and (3) a presently unknown sequence of events that must either lead to cell cycle arrest (G2-block, differentiation) or apoptosis. DNA degradation provides a convenient way to quantify apoptosis in HL-60 cells. Extensive apoptosis can be induced rapidly in undifferentiated HL-60 cells without prevention by cycloheximide or actinomycin D. Therefore, HL-60 cells appear to express constitutively the apoptotic machinery that may be kept under control of a yet unknown repressor. The absence of the tumor suppresser p53 and the presence of bcl-2 are in contrast with the sensitivity of these cells to apoptosis. Agents that modify chromatin structure (zinc, poly[ADPribose] inhibitors, spermine) can block DNA fragmentation without affecting cell survival. By contrast macrophagelike differentiation by phorbol esters suppresses apoptosis without affecting topoisomerase-induced DNA damage. Better understanding of the apoptotic regulation in the widely used and characterized HL-60 cell line should allow the identification of new mechanisms and parameters of cellular sensitivity and resistance to the cytotoxic activity of anticancer agents.

引用

页码：21 / 32

页数：12

共 143 条

[1]

Korsmeyer S.J., Bcl-2-An Antidote to Programmed Cell Death, Oncogenes in the Development of Leukaemia, 15, pp. 105-118, (1992)

[2]

Duke R.C., Chevernak R., Cohen J.J., Endogenous endonuclease-induced DNA fragmentation: An early event in cell-mediated cytolysis, Proc. Natl. Acad. Sci. USA, 80, pp. 6361-6365, (1983)

[3]

Martin S.J., Bradley J.G., Cotter T.G., HL-60 Cells induced to differentiate towards neutrophils subsequently die via apoptosis, Clin. Exp. Immunol., 79, pp. 448-453, (1990)

[4]

Colombel M., Olsson C.A., Ng P.Y., Buttyan R., Hormone-regulated apoptosis results from reentry of differentiated prostate cells onto a defective cell cycle, Can cer Res., 52, pp. 4313-4319, (1992)

[5]

Sellins K.S., Cohen J.J., Gene induction by gamma-irradiation leads to DNA fragmentation in lymphocytes, J. Immunol., 139, pp. 3199-3206, (1987)

[6]

McConkey D.J., Aguilar-Santelises M., Hartzell P., Eriksson I., Mellstedt H., Orrenius S., Jondal M., Induction of DNA fragmentation in chronic B-lymphocytic leukemia cells, J. Immunol., 146, pp. 1072-1076, (1991)

[7]

Barry M.A., Behnke C.A., Eastman A., Activation of programmed cell death (apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia, Biochem. Pharmacol., 40, pp. 2353-2362, (1990)

[8]

Kaufmann S.H., Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs: A cautionary note, Cancer Res., 49, pp. 5870-5878, (1989)

[9]

Fisher T.C., Milner A.E., Gregory C.D., Jackman A.L., Aherne G.W., Hartley J.A., Dive C., Hickman J.A., bcl-2 Modulation of apoptosis induced by anticancer drugs—Resistance to thymidylate stress is independent of classical resistance pathways, Cancer Res., 53, pp. 3321-3326, (1993)

[10]

Kamesaki S., Kamesaki H., Jorgensen T.J., Tanizawa A., Pommier Y., Cossman J., bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase II-induced DNA strand breaks and their repair, Cancer Res., 53, pp. 4251-4256, (1993)

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