Curcumin inhibits PhIP induced cytotoxicity in breast epithelial cells through multiple molecular targets

Ashok Jain, Abhilash Samykutty, Carissa Jackson, Darren Browning, Wendy B. Bollag, Muthusamy Thangaraju, Satoru Takahashi, Shree Ram Singh

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)122-131
Number of pages10
JournalCancer Letters
Volume365
Issue number1
DOIs
Publication statusPublished - Aug 28 2015

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Keywords

  • Cancer prevention
  • DNA adduct
  • DNA damage
  • Heterocyclic amines
  • Phytochemicals
  • Reactive oxygen species

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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