Department of Biochemistry, Basic Medical Science, Block-II, Sector-25, South Campus, Panjab University, Chandigarh, 160014, India.
Pharmacology and Toxicology Lab, Block J, CSIR-IHBT, Palampur, Himachal Pradesh, 176061, India.
Mol Cell Biochem. 2021 Apr;476(4):1765-1781. doi: 10.1007/s11010-020-04044-7. Epub 2021 Jan 12.
NF-κB is the principle transcription factor and plays the central role in orchestrating chronic inflammation by regulating levels of cytokines, chemokines and growth factors. Piperlongumine (PL), a major alkaloid in the fruit of Piper longum Linn. has gained worldwide attention for its anticancer properties, however, its mechanism of action in the chemoprevention of colon cancer has not been investigated yet. Therefore, the present study was designed to elucidate the underlying molecular mechanism of PL in preventing DMH/DSS induced experimental colon cancer in mice. In the current study well established DMH/DSS induced experimental colon cancer mouse model was used to demonstrate the chemopreventive potential of PL. The expression of NF-κB and its downstream target proteins was evaluated mainly through western blotting. In addition, CAM assay, immunohistochemical staining and gelatin zymography was used to show anti-angiogenic and anti-invasive potential of PL. Additionally, important tumor biomarkers such as TSA, LASA, LDH and IL-6 levels were also estimated. The results of current study showed that PL was capable to inhibit NF-κB activation as well as its nuclear translocation. PL administration to DMH/DSS treated mice also inhibited the NF-κB downstream signaling cascades such as including COX-2 pathway, JAK/STAT pathway, β-catenin, Notch signaling pathway, angiogenesis and epithelial to mesenchymal transition pathway. The findings of the present study have claimed PL as promising chemopreventive agent for colon cancer with pleiotropic action. The current study emphasizes that regular consumption of PL can be an effective approach in the prevention of colon cancer in humans.
NF-κB 是主要的转录因子，通过调节细胞因子、趋化因子和生长因子的水平，在调控慢性炎症中发挥核心作用。荜茇酰胺（PL）是胡椒科植物荜茇果实中的主要生物碱，因其抗癌特性而受到全球关注，但其在结肠癌化学预防中的作用机制尚未得到研究。因此，本研究旨在阐明 PL 在预防 DMH/DSS 诱导的实验性结肠癌中的潜在分子机制。在本研究中，使用了成熟的 DMH/DSS 诱导的实验性结肠癌小鼠模型来证明 PL 的化学预防潜力。通过 Western blot 主要评估 NF-κB 及其下游靶蛋白的表达。此外，还使用 CAM 试验、免疫组织化学染色和明胶酶谱法来显示 PL 的抗血管生成和抗侵袭潜力。此外，还评估了重要的肿瘤生物标志物，如 TSA、LASA、LDH 和 IL-6 水平。本研究结果表明，PL 能够抑制 NF-κB 的激活及其核易位。PL 给药于 DMH/DSS 处理的小鼠也抑制了 NF-κB 下游信号通路，如 COX-2 通路、JAK/STAT 通路、β-catenin、Notch 信号通路、血管生成和上皮间质转化通路。本研究的结果表明 PL 是一种有前途的结肠癌化学预防剂，具有多种作用。本研究强调，PL 的定期摄入可能是预防人类结肠癌的有效方法。
