Evaluation of the cytotoxic and antimutagenic effects of biflorin, an antitumor 1,4 o-naphthoquinone isolated from Capraria biflora L.
Biflorin is a natural quinone isolated from Capraria biflora L. Previous studies demonstrated that biflorin inhibits in vitro and in vivo tumor cell growth and presents potent antioxidant activity. In this paper, we report concentration-dependent cytotoxic, genotoxic, antimutagenic, and protective effects of biflorin on Salmonella tiphymurium, yeast Saccharomyces cerevisiae, and V79 mammalian cells, using different approaches. In the Salmonella/microsome assay, biflorin was not mutagenic to TA97a TA98, TA100, and TA102 strains. However, biflorin was able to induce cytotoxicity in haploid S. cerevisiae cells in stationary and exponential phase growth. In diploid yeast cells, biflorin did not induce significant mutagenic and recombinogenic effects at the employed concentration range. In addition, the pre-treatment with biflorin prevented the mutagenic and recombinogenic events induced by hydrogen peroxide (H(2)O(2)) in S. cerevisiae. In V79 mammalian cells, biflorin was cytotoxic at higher concentrations. Moreover, at low concentrations biflorin pre-treatment protected against H(2)O(2)-induced oxidative damage by reducing lipid peroxidation and DNA damage as evaluated by normal and modified comet assay using DNA glycosylases. Our results suggest that biflorin cellular effects are concentration dependent. At lower concentrations, biflorin has significant antioxidant and protective effects against the cytotoxicity, genotoxicity, mutagenicity, and intracellular lipid peroxidation induced by H(2)O(2) in yeast and mammalian cells, which can be attributed to its hydroxyl radical-scavenging property. However, at higher concentrations, biflorin is cytotoxic and genotoxic.
Vasconcellos
Marne C
MC
Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
Moura
Dinara J
DJ
Rosa
Renato M
RM
Machado
Miriana S
MS
Guecheva
Temenouga N
TN
Villela
Izabel
I
Immich
Bruna F
BF
Montenegro
Raquel C
RC
Fonseca
Aluísio M
AM
Lemos
Telma L G
TL
Moraes
Maria Elisabete A
ME
Saffi
Jenifer
J
Costa-Lotufo
Letícia V
LV
Moraes
Manoel O
MO
Henriques
João A P
JA
D000818:Animals; D016587:Antimutagenic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D002460:Cell Line; D020552:Comet Assay; D004354:Drug Screening Assays, Antitumor; D029624:Ferns / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D012475:Salmonella / Q000187:drug effects
D016587:Antimutagenic Agents; D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D009285:Naphthoquinones; C522781:biflorin