Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, Building, 62500 Brno, Czech Republic.
Toxicol In Vitro. 2010 Apr;24(3):697-706. doi: 10.1016/j.tiv.2010.01.012. Epub 2010 Feb 4.
Sanguilutine and chelilutine, quaternary benzo[c]phenanthridine alkaloids, were studied for their antiproliferative activities with regard to their ability to induce oxidative stress. We observed potent antiproliferative activities for both alkaloids against three tumour (HeLa; HL-60; A-2780) and two normal (V-79; LEP) cell lines. Both alkaloids were efficient inductors of apoptosis. Statistical analysis revealed higher toxicity for sanguilutine compared to chelilutine and unequal sensitivity with regard to individual cell lines, although independent of the character of the cell line (i.e. tumour vs. normal). Dihydrofluorescein diacetate staining was used to measure intracellular ROS accumulation after treatment with sanguilutine, chelilutine, sanguinarine, and chelerythrine. In addition, anti-oxidative effects were studied. The effects of the alkaloids were compared with the effects of commonly used anti-oxidants, such as trolox, caffeine acid, and chlorogenic acid. None of the tested alkaloids (0.1 and 1 microg/ml) increased ROS production. Pre-incubation of sanguinarine and chelilutine (at all tested concentrations) and sanguilutine and chelerythrine (1 microg/ml) decreased oxidative stress caused by H(2)O(2). These findings indicate high antiproliferative and pro-apoptotic effects of sanguilutine and chelilutine that are not accompanied by oxidative stress induction, to the contrary, both alkaloids showed anti-oxidative effects.
血根碱和Chelilutine，季铵苯并[c]菲啶生物碱，研究了它们的抗肿瘤活性与诱导氧化应激的能力。我们观察到两种生物碱对三种肿瘤（HeLa；HL-60；A-2780）和两种正常（V-79；LEP）细胞系均有较强的增殖抑制活性。两种生物碱都是有效的凋亡诱导剂。统计分析显示，血根碱的毒性高于 Chelilutine，并且对个别细胞系的敏感性不同，尽管与细胞系的性质无关（即肿瘤与正常）。二氢荧光素二乙酸酯染色用于测量经 sanguilutine、chelilutine、血根碱和白屈菜红碱处理后细胞内 ROS 的积累。此外，还研究了抗氧化作用。将生物碱的作用与常用抗氧化剂如 Trolox、咖啡酸和绿原酸的作用进行了比较。在测试的浓度下，没有一种生物碱（0.1 和 1μg/ml）增加了 ROS 的产生。血根碱和 Chelilutine（在所有测试浓度下）以及 sanguilutine 和 chelerythrine（1μg/ml）的预孵育降低了 H（2）O（2）引起的氧化应激。这些发现表明，血根碱和 Chelilutine 具有较高的增殖抑制和促凋亡作用，而不伴有氧化应激诱导，相反，两种生物碱均显示出抗氧化作用。
