The effects of curcumin on proliferation, apoptosis, invasion, and NEDD4 expression in pancreatic cancer

• Published in: Biochemical pharmacology Vol. 140; pp. 28 - 40
• Main Authors: Su, Jingna, Zhou, Xiuxia, Yin, Xuyuan, Wang, Lixia, Zhao, Zhe, Hou, Yingying, Zheng, Nana, Xia, Jun, Wang, Zhiwei
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 15.09.2017
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Curcumin; Curcumin - pharmacology; Endosomal Sorting Complexes Required for Transport - antagonists & inhibitors; Endosomal Sorting Complexes Required for Transport - genetics; Endosomal Sorting Complexes Required for Transport - metabolism; Enzyme Repression - drug effects; Humans; Inhibitory Concentration 50; Invasion; NEDD4; Nedd4 Ubiquitin Protein Ligases; Neoplasm Invasiveness; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; PTEN Phosphohydrolase - chemistry; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; Reactive Oxygen Species - agonists; Reactive Oxygen Species - metabolism; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; RNA Interference; Tumor Protein p73 - agonists; Tumor Protein p73 - genetics; Tumor Protein p73 - metabolism; Ubiquitin-Protein Ligases - antagonists & inhibitors; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Up-Regulation - drug effects; Cell growth; Curcumin; Pancreatic cancer; NEDD4; Invasion
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2017.05.014

[Display omitted] Pancreatic cancer (PC) is one of the most fatal cancers worldwide. The incidence and death rates are still increasing for PC. Curcumin is the biologically active diarylheptanoid constituent of the spice turmeric, which exerts its anticancer properties in various human cancers including PC. In particular, accumulating evidence has proved that curcumin targets numerous therapeutically important proteins in cell signaling pathways. The neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) is an E3 HECT ubiquitin ligase and is frequently over-expressed in various cancers. It has reported that NEDD4 might facilitate tumorigenesis via targeting and degradation of multiple tumor suppressor proteins including PTEN. Hence, in the present study we explore whether curcumin inhibits NEDD4, resulting in the suppression of cell growth, migration and invasion in PC cells. We found that curcumin inhibited cell proliferation and triggered apoptosis in PC, which is associated with increased expression of PTEN and p73. These results suggested that inhibition of NEDD4 might be beneficial to the antitumor properties of curcumin on PC treatments.