Jain Ashok, Samykutty Abhilash, Jackson Carissa, Browning Darren, Bollag Wendy B, Thangaraju Muthusamy, Takahashi Satoru, Singh Shree Ram
Department of Natural Sciences, Albany State University, Albany, Georgia 31705, USA.
Department of Natural Sciences, Albany State University, Albany, Georgia 31705, USA.
Cancer Lett. 2015 Aug 28;365(1):122-31. doi: 10.1016/j.canlet.2015.05.017. Epub 2015 May 21.
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.
氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP）存在于熟肉中，是一种已知的食物致癌物，可引发多种癌症，包括乳腺癌，因为PhIP代谢产物会产生DNA加合物并导致DNA链断裂。姜黄素是从姜黄根茎中提取的，具有强大的抗癌活性。迄今为止，尚无研究探讨PhIP与姜黄素在乳腺上皮细胞中的相互作用。本研究揭示了姜黄素抑制正常乳腺上皮细胞（MCF-10A）中PhIP诱导的细胞毒性的机制。姜黄素显著抑制PhIP诱导的DNA加合物形成和DNA双链断裂，同时活性氧（ROS）生成减少。研究了Nrf2、FOXO靶标、DNA修复基因BRCA-1、H2AFX和PARP-1以及肿瘤抑制因子P16的表达，以评估对这些核心信号通路的影响。PhIP诱导了多种抗氧化和DNA修复基因的表达。然而，与姜黄素共同处理可抑制这种表达。PhIP抑制了肿瘤抑制因子P16基因的表达，而与姜黄素共同处理则增加了其表达。姜黄素轻微抑制了半胱天冬酶-3和-9，从而抑制了细胞死亡。这些结果表明，姜黄素似乎是一种有效的抗PhIP食品添加剂，可能通过多个分子靶点发挥作用。
