Publication details

Sanguinarine is reduced by NADH through a covalent adduct

Authors

SÁNDOR Roman SLANINA Jiří MIDLIK Adam ŠEBRLOVÁ Kristýna NOVOTNÁ Lucie ČARNECKÁ Martina SLANINOVÁ Iva TÁBORSKÝ Petr TÁBORSKÁ Eva PEŠ Ondřej

Type Article in Periodical
Magazine / Source Phytochemistry
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1016/j.phytochem.2017.10.010
Field Biochemistry
Keywords Benzophenanthridine alkaloids; Ene adduct; Hydride transfer; LC-MS; NADH; NADH depletion; Redox cycling; Sanguinarine
Description Sanguinarine is a benzo[c]phenanthridine alkaloid with interesting cytotoxic properties, such as induction of oxidative DNA damage and very rapid apoptosis, which is not mediated by p53-dependent signaling. It has been previously documented that sanguinarine is reduced with NADH even in absence of any enzymes while being converted to its dihydro form. We found that the dark blue fluorescent species, observed during sanguinarine reduction with NADH and misinterpreted by Matkar et al. (Arch. Biochem. Biophys. 2008, 477, 43–52) as an anionic form of the alkaloid, is a covalent adduct formed by the interaction of NADH and sanguinarine. The covalent adduct is then converted slowly to the products, dihydrosanguinarine and NAD+, in the second step of reduction. The product of the reduction, dihydrosanguinarine, was continually re-oxidized by the atmospheric oxygen back to sanguinarine, resulting in further reacting with NADH and eventually depleting all NADH molecules. The ability of sanguinarine to diminish the pool of NADH and NADPH is further considered when explaining the sanguinarine-induced apoptosis in living cells.
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