Impact of Curcumin, Raspberry Extract, and Neem Leaf Extract on Rel Protein-Regulated Cell Death/Radiosensitization in Pancreatic Cancer Cells
Impact of Curcumin, Raspberry Extract, and Neem Leaf Extract on Rel Protein-Regulated Cell Death/Radiosensitization in Pancreatic Cancer Cells
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DOI：
10.1097/mpa.0b013e31821f677d
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发表时间：
2011-10-01
期刊：
影响因子：
2.9
通讯作者：
Aravindan, Natarajan
中科院分区：
文献类型：
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作者：
Veeraraghavan, Jamunarani;Natarajan, Mohan;Aravindan, Natarajan
目的：核因子-kappaB在促进胰腺癌生长、血管生成和转移中起着重要的作用，是胰腺癌耐药的机制之一。方法：PANC-1、BxPC-3和MIA Paca-2细胞分别接受10GY(单次高剂量[SDR])或2GY/d(分次照射[FIR])5d(分次照射[FIR])和/或联合姜黄素(Cur)、印楝叶提取物(NLE)和黑树莓提取物(RSE)诱导的NF-kappa B-DNA结合活性的检测。姜黄素、NLE和RSE显著抑制原始性和RT诱导的NF-kappa B。此外，对88个NF-kappa B途径分子的定量聚合酶链式反应图谱表明，Cur、NLE和RSE全面但不同地抑制FIR/SDR诱导的基因。在功能上，Cur、NLE和RSE显著地赋予RT抑制的细胞存活/存活，强烈激活caspase-3/7活性，以及随后的细胞死亡。更重要的是，核转录因子-kappaB的过表达和沉默研究表明，这些化合物通过靶向RT诱导的核因子-kappa B而增强RT诱导的细胞死亡。结论：这些数据强烈暗示Cur、NLE和RSE可能作为有效的“递送物”在PC CURE中增强RT，并进一步揭示这些植物化学物质诱导的细胞杀伤可能涉及到对RT诱导的核因子-kappa B的选择性调节。
Objectives: Nuclear factor kappa B (NF-kappa B) plays an intrinsic role in promoting growth, angiogenesis, and metastasis in pancreatic cancer (PC) and serves as a mechanism underlying therapeutic resistance. Accordingly, we investigated the efficacy of bioactive phytochemicals in inhibiting radiotherapy (RT)-induced NF-kappa B activity, signaling, and NF-kappa B-dependent regulation of cell death.Methods: Panc-1, BxPC-3, and MIA PaCa-2 cells exposed to 10 Gy (single high dose [SDR]) or 2 Gy/d for 5 days (fractionated radiation [FIR]) with or without curcumin (CUR), neem leaf extract (NLE), or black raspberry extract (RSE) were analyzed.Results: Radiotherapy profoundly induced NF-kappa B-DNA-binding activity with relatively robust activation after FIR. Curcumin, NLE, and RSE significantly inhibited both constitutive and RT-induced NF-kappa B. Furthermore, quantitative polymerase chain reaction profiling of 88 NF-kappa B pathway molecules demonstrated that CUR, NLE, and RSE comprehensively, yet differentially inhibited FIR/SDR-induced genes. Functionally, CUR, NLE, and RSE markedly conferred RT-inhibited cell viability/survival, robustly activated caspase-3/7 activity, and subsequent cell death. More importantly, NF-kappa B overexpression and silencing studies demonstrate that these compounds potentiate RT-induced cell death by targeting RT-induced NF-kappa B.Conclusions: These data strongly imply that CUR, NLE, and RSE may serve as effective "deliverables" to potentiate RT in PC cure and further throw light that these phytochemicals-induced cell killing may involve selective regulation of RT-induced NF-kappa B.