Verminoside- and verbascoside-induced genotoxicity on human lymphocytes: involvement of PARP-1 and p53 proteins.
Verminoside and verbascoside are natural compounds present in plants used in traditional medicine. They exhibit several biological activities including anti-inflammatory, anti-bacterial and anti-tumor properties. The potential applications of these compounds as ingredients in pharmaceutical formulations and cosmetics prompted us to investigate on cytotoxic and genotoxic activity of verminoside and verbascoside on human lymphocytes using genetic toxicity assays recommended in preclinical studies by the US Food and Drug Administration (FDA). We analyzed chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) as well as the mitotic index (MI) and cell viability after the treatments with verminoside and verbascoside. This report is the first to clearly demonstrate a significant increase of structural CAs and SCEs on normal human lymphocytes associated with a reduction of the MI in both verminoside- and verbascoside-treated cells. Moreover, we observed enhanced protein expression levels of PARP-1 and p53 that are key regulatory proteins involved in cell proliferation and DNA repair. Interestingly, mass spectrometric analysis of the compounds in the culture supernatants also showed that verminoside remained unchanged during the culture period while verbascoside was hydrolyzed to its derivative, caffeic acid and the last one seems to be responsible for the observed biological activity.
Santoro
Antonietta
A
Department of Pharmaceutical Sciences, University of Salerno, Via Ponte don Melillo, 84084 Fisciano, Salerno, Italy.
Bianco
Giuseppe
G
Picerno
Patrizia
P
Aquino
Rita Patrizia
RP
Autore
Giuseppina
G
Marzocco
Stefania
S
Gazzerro
Patrizia
P
Lioi
Maria Brigida
MB
Bifulco
Maurizio
M
D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations / Q000187:drug effects; D002875:Chromosomes / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000633:toxicity*; D006801:Humans; D039823:Iridoids / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008940:Mitotic Index; D009153:Mutagens; D010636:Phenols / Q000633:toxicity*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis* / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D059808:Polyphenols
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000972:Antineoplastic Agents, Phytogenic; D005960:Glucosides; D039823:Iridoids; D009153:Mutagens; D010636:Phenols; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D016159:Tumor Suppressor Protein p53; C506490:verminoside; C058956:acteoside; D059808:Polyphenols; C499320:PARP1 protein, human