Effects of Black Raspberry Extract and Protocatechuic Acid on Carcinogen-DNA Adducts and Mutagenesis, and Oxidative Stress in Rat and Human Oral Cells.
Effects of black raspberry (BRB) extract and protocatechuic acid (PCA) on DNA adduct formation and mutagenesis induced by metabolites of dibenzo[a,l]pyrene (DBP) were investigated in rat oral fibroblasts. The DBP metabolites, (±)-anti-11,12-dihydroxy-11,12,-dihydrodibenzo[a,l]pyrene (DBP-diol) and 11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DBPDE) induced dose-dependent DNA adducts and mutations. DBPDE was considerably more potent, whereas the parent compound had no significant effect. Treatment with BRB extract (BRBE) and PCA resulted in reduced DBP-derived DNA adduct levels and reduced mutagenesis induced by DBP-diol, but only BRBE was similarly effective against (DBPDE). BRBE did not directly inactivate DBPDE, but rather induced a cellular response-enhanced DNA repair. When BRBE was added to cells 1 day after the DBP-diol, the BRBE greatly enhanced removal of DBP-derived DNA adducts. As oxidative stress can contribute to several stages of carcinogenesis, BRBE and PCA were investigated for their abilities to reduce oxidative stress in a human leukoplakia cell line by monitoring the redox indicator, 2',7'-dichlorodihydrofluorescein diacetate (H2DCF) in cellular and acellular systems. BRBE effectively inhibited the oxidation, but PCA was only minimally effective against H2DCF. These results taken together provide evidence that BRBE and PCA can inhibit initiation of carcinogenesis by polycyclic aromatic hydrocarbons; and in addition, BRBE reduces oxidative stress. Cancer Prev Res; 9(8); 704-12. ©2016 AACR.
Department of Basic Science, New York University College of Dentistry, New York, New York. Department of Environmental Medicine, New York University School of Medicine, New York, New York. joseph.guttenplan@nyu.edu kelbayoumy@hmc.psu.edu.
Joseph B
JB
Guttenplan
Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania.
Kun-Ming
KM
Chen
Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania.
Yuan-Wan
YW
Sun
Department of Basic Science, New York University College of Dentistry, New York, New York.
Wieslawa
W
Kosinska
Department of Basic Science, New York University College of Dentistry, New York, New York.
Ying
Y
Zhou
Department of Basic Science, New York University College of Dentistry, New York, New York.
Seungjin Agatha
SA
Kim
Department of Basic Science, New York University College of Dentistry, New York, New York.
Youngjae
Y
Sung
Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania.
Krishne
K
Gowda
Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania.
Shantu
S
Amin
Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Gary D
GD
Stoner
Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania. joseph.guttenplan@nyu.edu kelbayoumy@hmc.psu.edu.
Karam
K
El-Bayoumy
D000818:Animals; D001580:Benzopyrenes / Q000633:toxicity; D063646:Carcinogenesis / Q000187:drug effects* / Q000235:genetics; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D018736:DNA Adducts / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology*; D009055:Mouth / Q000187:drug effects*; D009062:Mouth Neoplasms / Q000517:prevention & control; D016296:Mutagenesis / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010610:Pharyngeal Neoplasms / Q000517:prevention & control; D064209:Phytochemicals / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D065856:Rubus / Q000737:chemistry*; D013997:Time Factors
D001580:Benzopyrenes; D002273:Carcinogens; D018736:DNA Adducts; D062385:Hydroxybenzoates; D064209:Phytochemicals; D010936:Plant Extracts; C009091:protocatechuic acid