Modulating activity of fullerol C60(OH)22 on doxorubicin-induced cytotoxicity

Modulating activity of fullerol C60(OH)22 on doxorubicin-induced cytotoxicity
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DOI:
10.1016/j.tiv.2004.02.010
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发表时间:
2004-10-01
影响因子:
3.2
通讯作者:
Baltic, VV
Baltic, VV
中科院分区:
医学3区
文献类型:
--
作者:
Bogdanovic, G;Kojic, V;Baltic, VV

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本文报道了新合成的富勒醇C-60(OH)(22)对体外肿瘤细胞生长的影响及其对阿霉素(DOX)诱导的人乳腺癌细胞株细胞毒的调节作用。四唑盐比色法检测细胞生长抑制作用。用电子自旋共振(ESR)“捕集”方法研究了富勒醇在Fenton‘s反应中清除OH-自由基的活性。在一定的纳摩尔浓度范围内,富勒醇对细胞生长有抑制作用,这种抑制作用与细胞系、剂量和时间有关。无论加入富勒醇的时间长短,富勒醇在所有浓度下都能强烈抑制DOX诱导的细胞毒作用。原花青素单独作用于MCF-7细胞48h后,细胞生长抑制率较低,但与DOX联合使用时,DOX的细胞毒作用明显减弱。富勒醇是一种有效的羟基自由基清除剂:当富勒醇浓度为0.5µg/ml时,DMPO-羟基自由基自旋加合物的ESR信号相对强度降低了88%。这些结果表明,富勒醇的抗增殖作用和对DOX细胞毒性的保护作用可能是通过清除C-60(OH)(22)的羟基自由基活性来实现的。(C)2004爱思唯尔有限公司。保留所有权利。
Paper presents the effects of the newly synthesized fullerol C-60(OH)(22) on the growth of tumor cells in vitro and its modulating activity on doxorubicin (DOX)-induced cytotoxicity in human breast cancer cell lines. Cell growth inhibition was evaluated by tetrazolium colorimetric WST1 assay. Electron spin resonance (ESR) "trapping" method was used to investigate OH-radical scavenger activity of fullerol during Fenton's reaction. At a range of nanomolar concentrations fullerol induced cell growth inhibition, which was cell line, dose and time dependent. Fullerol also strongly suppressed DOX-induced cytotoxicity at all concentrations regardless the time of fullerol addition. Proanthocyanidins added as single agent to MCF-7 cell culture for 48 h induced low growth inhibition but in combination with DOX strongly decreased DOX cytotoxicity. Fullerol was found to be a potent hydroxyl radical scavenger: the relative intensity of ESR signals of DMPO-hydroxyl radical (DMPO-OH) spin adduct decreased by 88% in the presence of 0.5 mug/ml of fullerol. The obtained results suggest that antiproliferative effect of the fullerol and its protective effect on DOX-induced cytotoxicity might be mediated through hydroxyl-radical scavenger activity of C-60(OH)(22). (C) 2004 Elsevier Ltd. All rights reserved.