Protective effect of phosphatidylcholine on lysophosphatidylcholine‐induced cellular senescence in cholangiocyte. (2nd November 2019)

• Record Type: Journal Article
• Authors: Ohigashi, Toshikazu; Kanno, Keishi; Sugiyama, Akiko; Nguyen, Phuong Thao; Kishikawa, Nobusuke; Otani, Yuichiro; Kobayashi, Tomoki; Matsuo, Hiroaki; Tazuma, Susumu
• Is Part Of: Journal of hepato-biliary-pancreatic sciences. Volume 26:Number 12(2019)
• Page Start: 568
• Page End: 577
• Publication Date: 2019-11-02
• Subjects: Cholangiocarcinoma -- Epithelial to mesenchymal transition -- Lysophosphatidylcholine -- Phosphatidylcholine -- Senescence‐associated secretory phenotype; Liver -- Diseases -- Periodicals; Biliary tract -- Diseases -- Periodicals; Pancreas -- Diseases -- Periodicals; 617.556
• DOI: 10.1002/jhbp.684
• Languages: English
• ISSNs: 1868-6974

Abstract

Abstract: Background: Pancreaticobiliary maljunction and intrahepatic gallstones are at a high risk for biliary malignancy. Lysophosphatidylcholine (LPC) is increased in the bile of these patients, and we have previously reported that LPC‐induced cytotoxicity causes senescence‐associated secretory phenotype (SASP) in cholangiocytes. We aimed to determine the protective effect of phosphatidylcholine (PC) on LPC‐induced cholangiocyte cytotoxicity. Methods: MMNK‐1, a human immortalized cholangiocyte cell line was treated with LPC with or without PC. To assess the biological effects of SASP components on cholangiocarcinoma, HuH28 and HuCCT1 (human cholangiocarcinoma cell lines) were cultured in the conditioned media where MMNK‐1 cells treated with LPC. Results: The presence of PC reduced reactive oxygen species generation and oxidative DNA damage in MMNK‐1 treated with LPC. Moreover, SA‐β‐gal activity was markedly downregulated by PC. The secretion of SASP components, including interleukin (IL)‐8, IL‐6, and C‐C motif chemokine ligand 2 was also substantially reduced in the presence of PC. Cellular proliferation and migration were enhanced in HuCCT1 and HuH28 cells when cultured in the conditioned media, and these observations were suppressed by simultaneous addition of PC. Conclusion: PC protects cholangiocytes against LPC‐induced cytotoxicity and cellular senescence, suggesting its potential as a target for inhibiting LPC‐related carcinogenesis and its promotion. Abstract : Highlight Pancreaticobiliary maljunction with intrahepatic gallstones is a high‐risk factor for biliary malignancy. The bile in this condition has increased amounts of lysophosphatidylcholine (LPC), which induces cytotoxicity causing the senescence‐associated secretory phenotype of cholangiocytes. Ohigashi and colleagues established that phosphatidylcholine protects cholangiocytes against LPC‐induced cytotoxicity and cellular senescence, and inhibits LPC‐related carcinogenesis.