Evaluation of the genotoxicity of piplartine, an alkamide of Piper tuberculatum, in yeast and mammalian V79 cells

The genus Piper belongs to the Piperaceae family, and includes species of commercial and medicinal importance. Chemical studies on species resulted in the isolation of several biologically active molecules, including alkaloid amides, such as piplartine. This molecule, from Piper tuberculatum, has significant cytotoxic activity against tumor cell lines, and presents antifungal, anti-platelet aggregation, and antidepressant effects. In order to understand the biological properties of piplartine, this study investigated the genotoxicity and the of apoptosis by piplartine in V79 cells and its mutagenic and recombinogenic potential in Saccharomyces cerevisiae. Piplartine induced dependent cytotoxicity in S. cerevisiae cultures in either stationary-or exponential growth phase. In addition, piplartine was not mutagenic cells were treated during exponential-growth phase and kept in buffer solution, but it increased the frequencies of point, frameshift, and mutations when cells were treated in medium during growth, Piplartine treatment induced DNA strand breaks in V79 cells, as detected by and alkaline comet assay. In cell cycle analysis, piplartine induced G2/M cell cycle arrest, probably as a consequence of the DNA damage and repair. Moreover, piplartine treatment induced apoptosis in a dose-dependent manner, as observed by a decrease in mitochondrial potential and an increase in internucleosomal DNA fragmentation. These data suggest that the DNA damage caused by piplartine induces cell cycle arrest, followed by apoptosis. Moreover, we suggest that cells surviving piplartine-induced DNA damage can accumulate since this alkaloid was mutagenic and recombinogenic in S. cerevisiae assays. (C) 2008 Elsevier B.V. All rights reserved.