Morré D J, Morré D M, Wu L Y
Department of Medicinal Chemistry, Purdue University, West Lafayette, Indiana 47907.
J Bioenerg Biomembr. 1994 Feb;26(1):137-42. doi: 10.1007/BF00763225.
Adriamycin, 10(-8) - 10(-5) M, inhibited transplasma membrane electron transport of uninduced HL-60 cells susceptible to adriamycin and not in uninduced HL-60 cells resistant to adriamycin as measured by reduction of external ascorbate free radical. Electron flow across the plasma membrane was measured with the intact living cells by means of a simple assay procedure whereby the transported electrons were captured by ascorbate free radical to slow the rate of chemical oxidation of ascorbate. The response to adriamycin was rapid with maximum inhibition in less than 1 min. Preincubation was not required and the inhibition presumably was not mediated through effects on DNA replication or transcription. Except at the highest concentration tested of 10 microM, both transplasma membrane electron transport and growth were unaffected by adriamycin with a line of HeLa cells resistant to the drug. The findings provide evidence, using a physiological acceptor, ascorbate free radical, for a direct inhibition of transmembrane electron transport of HL-60 cells by adriamycin that correlates closely with adriamycin inhibition of cell growth. The lack of response with resistant cells suggests an alternative mechanism for adriamycin resistance not necessarily based on transport control.
阿霉素，浓度为10(-8)-10(-5)M时，可抑制对阿霉素敏感的未诱导HL-60细胞的跨质膜电子传递，而对阿霉素耐药的未诱导HL-60细胞则无此作用，这是通过细胞外抗坏血酸自由基的还原进行测定的。通过一种简单的检测方法，利用完整的活细胞测量跨质膜的电子流，在此过程中，转运的电子被抗坏血酸自由基捕获，以减缓抗坏血酸的化学氧化速率。对阿霉素的反应迅速，不到1分钟即达到最大抑制。无需预孵育，且这种抑制作用可能不是通过对DNA复制或转录的影响介导的。除了在测试的最高浓度10微摩尔时，对阿霉素耐药的HeLa细胞系的跨质膜电子传递和生长均不受阿霉素影响。这些发现提供了证据，即利用生理受体抗坏血酸自由基，阿霉素可直接抑制HL-60细胞的跨膜电子传递，这与阿霉素对细胞生长的抑制密切相关。耐药细胞无反应表明阿霉素耐药存在一种不一定基于转运控制的替代机制。
