title: Curcumin inhibits PhIP induced cytotoxicity in breast epithelial cells through multiple molecular targets.
abstract: Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), found in cooked meat, is a known food carcinogen that causes several types of cancer, including breast cancer, as PhIP metabolites produce DNA adduct and DNA strand breaks. Curcumin, obtained from the rhizome of Curcuma longa, has potent anticancer activity. To date, no study has examined the interaction of PhIP with curcumin in breast epithelial cells. The present study demonstrates the mechanisms by which curcumin inhibits PhIP-induced cytotoxicity in normal breast epithelial cells (MCF-10A). Curcumin significantly inhibited PhIP-induced DNA adduct formation and DNA double stand breaks with a concomitant decrease in reactive oxygen species (ROS) production. The expression of Nrf2, FOXO targets; DNA repair genes BRCA-1, H2AFX and PARP-1; and tumor suppressor P16 was studied to evaluate the influence on these core signaling pathways. PhIP induced the expression of various antioxidant and DNA repair genes. However, co-treatment with curcumin inhibited this expression. PhIP suppressed the expression of the tumor suppressor P16 gene, whereas curcumin co-treatment increased its expression. Caspase-3 and -9 were slightly suppressed by curcumin with a consequent inhibition of cell death. These results suggest that curcumin appears to be an effective anti-PhIP food additive likely acting through multiple molecular targets.
authors.affiliation: Department of Natural Sciences, Albany State University, Albany, Georgia 31705, USA. Electronic address: ashok.jain@asurams.edu.
authors.forename: Ashok
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Natural Sciences, Albany State University, Albany, Georgia 31705, USA.
authors.forename: Abhilash
authors.initials: A
authors.lastname: Samykutty
authors.affiliation: Department of Natural Sciences, Albany State University, Albany, Georgia 31705, USA.
authors.forename: Carissa
authors.initials: C
authors.lastname: Jackson
authors.affiliation: Cancer Center, Georgia Regents University, Augusta, Georgia 30912, USA.
authors.forename: Darren
authors.initials: D
authors.lastname: Browning
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, Georgia 30912, USA; Charlie Norwood VA Medical Center, Augusta, Georgia 30904, USA.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Bollag
authors.affiliation: Cancer Center, Georgia Regents University, Augusta, Georgia 30912, USA.
authors.forename: Muthusamy
authors.initials: M
authors.lastname: Thangaraju
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA. Electronic address: singhshr@mail.nih.gov.
authors.forename: Shree Ram
authors.initials: SR
authors.lastname: Singh
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D019610:Cytoprotection; D018736:DNA Adducts / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000633:toxicity*; D042361:Mammary Glands, Human / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D018736:DNA Adducts; D007093:Imidazoles; D017382:Reactive Oxygen Species; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D003474:Curcumin
keywords: Cancer prevention; DNA adduct; DNA damage; Heterocyclic amines; Phytochemicals; Reactive oxygen species