Effect of quaternary benzo[c]phenanthridine alkaloids sanguilutine and chelilutine on normal and cancer cells.
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.
Slunská
Z
Z
Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, Building, 62500 Brno, Czech Republic.
Gelnarová
E
E
Hammerová
J
J
Táborská
E
E
Slaninová
I
I
D017304:Annexin A5; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D053119:Benzophenanthridines / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004396:Coloring Agents; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D020287:In Situ Nick-End Labeling; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D011419:Propidium; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
D017304:Annexin A5; D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D004396:Coloring Agents; D016877:Oxidants; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; C550176:chelilutine; C550175:sanguilutine; D011419:Propidium; D006861:Hydrogen Peroxide; C022616:thiazolyl blue