In vitro evaluation of newly developed chalcone analogues in human cancer cells
In vitro evaluation of newly developed chalcone analogues in human cancer cells
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DOI：
10.1007/s002800000160
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发表时间：
2000-10-01
影响因子：
3
通讯作者：
Scambia, G
中科院分区：
文献类型：
--
作者：
De Vincenzo, R;Ferlini, C;Scambia, G
目的：在黄酮类化合物中，查耳酮是一类具有化学预防和抗肿瘤活性的化合物。我们使用MDA-MB 231和MCF-7 ADRr乳腺癌细胞和T-白血病Jurkat细胞系研究了一组新开发的查耳酮类似物（S1-S10）。槲皮素用作参比化合物。方法：通过暴露于药物72小时后进行的细胞计数来评价抗增殖活性。使用流式细胞术评估DNA分析和氧化还原活性。细胞凋亡进行了评估，通过形态学分析，使用YOYO-1作为DNA染料，P-糖蛋白的功能，通过定量罗丹明123的流出确定。结果如下：所有细胞均对查耳酮类似物敏感，产生微摩尔浓度的IC 50，无论多药耐药（MDR）状态如何，顺序如下：S1 > S2 >槲皮素。选择活性最高的化合物S1和S2，以评价其对细胞周期、凋亡、氧化还原活性和P-糖蛋白功能调节的影响。24小时后，浓度高达1 μ M时，未观察到细胞周期的显著扰动。72小时后，G（2）/M阻滞和DNA断裂在10 μ M时略有增加。细胞凋亡的形态学分析表明，查尔酮类似物：诱导细胞凋亡的程度高于槲皮素。氧化还原分析表明，所有的物质都能够增加细胞内巯基水平，除了槲皮素，所有药物在24小时后恢复到基线值。活性氧的产生基本上不受所有化合物的影响。最后，在MDR阳性MCF-7 ADRr细胞中，查耳酮类似物不能调节P-糖蛋白功能，而槲皮素能够。结论：新开发的S1和S2查尔酮具有与槲皮素不同但更高的抗肿瘤活性，可被认为是潜在的新型抗肿瘤药物。
Purpose: Among flavonoids, chalcones have been identified as interesting compounds having chemopreventive and antitumor properties. We studied a panel of newly developed chalcone analogues (S1-S10) using MDA-MB 231 and MCF-7 ADRr breast cancer cells and the T-leukemic Jurkat cell line. Quercetin was used as the reference compound. Methods: Antiproliferative activity was evaluated by cell counts performed after 72 h of exposure to the drugs. DNA analysis and redox activity were evaluated using flow cytometry. Apoptosis was assessed by morphological analysis, using YOYO-1 as DNA dye; p-glycoprotein function was ascertained by quantitating the efflux of rhodamine 123. Results: All cells were sensitive to chalcone analogues yielding IC50 in micromolar concentrations with the following order regardless of the multidrug resistance (MDR) status: S1 > S2 > quercetin. S1 and S2, the most active compounds, were selected to evaluate their effect on the cell cycle, apoptosis, redox activity, and modulation of the p-glycoprotein function. No significant perturbation in cell cycle was seen with concentration up to 1 mu M after 24 h. After 72 h a slight increase in G(2)/M block and DNA fragmentation occurred at 10 mu M. Morphological analysis of apoptosis showed that chalcone analogues: induced apoptosis to a higher extent than quercetin. Redox analysis demonstrated that all substances were able to increase intracellular thiol levels, which returned to baseline value after 24 h for all drugs except quercetin. Production of reactive oxygen species was essentially unaffected by all compounds. Finally, in MDR-positive MCF-7 ADRr cells chalcone analogues were unable to modulate p-glycoprotein function while quercetin was able to. Conclusions: Newly developed S1 and S2 chalcones have a different but higher antitumor activity than quercetin and could be considered as potential new anticancer drugs.