Effect of quaternary benzo[c]phenanthridine alkaloids sanguilutine and chelilutine on normal and cancer cells

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Year of publication 2010
Type Article in Periodical
Magazine / Source Toxicology in Vitro
MU Faculty or unit

Faculty of Medicine

Web http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCP-4Y9SVS3-1&_user=835458&_coverDate=04%2F30%2F2010&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000045159&_version=1&_urlVersion=0&_userid=835458&md5=fb5acce5418506b30b592a4
Field Genetics and molecular biology
Keywords benzo(c)phenanthridine alkaloids; sanguilutine; chelilutine; cytotoxicity; oxidative stress; antioxidant
Description Sanguilutine and chelilutine, quaternary benzo[c]phenanthridine alkaloids, were studied for their anti-proliferative activities with regard to their ability to induce oxidative stress. We observed potent anti-proliferative activities for both alkaloids against three tumor (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 an unequal sensitivity with regard to individual cell lines but independent of the character of the cell line (i.e. tumor vs. normal). Dihydrofluorescein diacetate staining was used for measurement of intracellular ROS accumulation, not only after sanguilutine and chelilutine, but also after sanguinarine and chelerythrine treatment. In addition the antioxidative effect was studied. The effect of the alkaloids was compared with the effect of commonly used antioxidants such as trolox, caffeine acid, and chlorogenic acid. All tested alkaloids, at concentrations of 0.1 and 1 ug/ml, did not increase ROS production. However, pre-incubation with all alkaloids, at all tested concentrations, with the exception of sanguilutine and chelerythrine at 1 ug/ml, decreased oxidative stress caused by H2O2. These findings indicate high anti-proliferative 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.
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