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Onco Targets Ther. 2015 Dec 01;8:3585-93. doi: 10.2147/OTT.S92832. eCollection 2015.

Inhibitive effects of 15-deoxy-Δ(12),(14)-prostaglandin J2 on hepatoma-cell proliferation through reactive oxygen species-mediated apoptosis.

OncoTargets and therapy

Kan Chen, Weiqi Dai, Fan Wang, Yujing Xia, Jingjing Li, Sainan Li, Tong Liu, Rong Zhang, Jianrong Wang, Wenxia Lu, Yuqing Zhou, Qin Yin, Yuanyuan Zheng, Huerxidan Abudumijiti, Rongxia Chen, Jie Lu, Yingqun Zhou, Chuanyong Guo

Affiliations

  1. Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
  2. Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, First Clinical Medical College of Nanjing Medical University, Nanjing, People's Republic of China.
  3. Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.

PMID: 26664142 PMCID: PMC4671813 DOI: 10.2147/OTT.S92832

Abstract

OBJECTIVE: 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) induces reactive oxygen species (ROS)-mediated apoptosis in many malignant cells, which has not been studied in hepatoma cells. In this study, we investigated whether 15d-PGJ2 induced apoptosis in hepatocellular carcinoma (HCC) associated with ROS.

MATERIALS AND METHODS: The LM3, SMMC-7721, and Huh-7 HCC cell lines were treated with 15d-PGJ2 (5-40 μM) for 24, 48, and 72 hours. Cholecystokinin 8 was used to detect the cytotoxicity of 15d-PGJ2. Flow cytometry, Hoechst staining, and Western blotting were used to analyze apoptosis. ROS were combined with the fluorescent probe dihydroethidium and then observed by fluorescence microscopy and flow cytometry. Activation of JNK and expression of Akt were detected by Western blotting.

RESULTS: 15d-PGJ2 inhibited HCC cell proliferation and induced apoptosis in a dose- and time-dependent manner. Apoptosis was mainly induced via an intrinsic pathway and was ROS-dependent, and was alleviated by ROS scavengers. ROS induced JNK activation and Akt downregulation in HCC cells.

CONCLUSION: 15d-PGJ2 induced ROS in HCC cell lines, and inhibition of cell growth and apoptosis were partly ROS-dependent.

Keywords: 15-deoxy-Δ12,14-prostaglandin J2; JNK; ROS; apoptosis; hepatoma cell

References

  1. Prostaglandins Leukot Essent Fatty Acids. 1992 Sep;47(1):1-12 - PubMed
  2. World J Gastroenterol. 2003 Aug;9(8):1683-8 - PubMed
  3. PLoS One. 2014 May 09;9(5):e97414 - PubMed
  4. Cancer Res. 1991 Feb 1;51(3):794-8 - PubMed
  5. J Biol Chem. 2002 Aug 30;277(35):31963-71 - PubMed
  6. Clin Cancer Res. 2009 Sep 1;15(17):5414-25 - PubMed
  7. Apoptosis. 2007 Nov;12(11):2101-14 - PubMed
  8. Nat Rev Mol Cell Biol. 2007 Oct;8(10):813-24 - PubMed
  9. J Cell Sci. 2003 Aug 1;116(Pt 15):3051-60 - PubMed
  10. Biochem J. 2010 Aug 15;430(1):69-78 - PubMed
  11. Nature. 2000 Nov 9;408(6809):239-47 - PubMed
  12. Exp Ther Med. 2015 Apr;9(4):1413-1420 - PubMed
  13. PPAR Res. 2013;2013:751261 - PubMed
  14. Free Radic Biol Med. 2011 Apr 1;50(7):854-65 - PubMed
  15. Toxicology. 2008 Jun 27;248(2-3):121-9 - PubMed
  16. Chem Res Toxicol. 2008 Jan;21(1):138-44 - PubMed
  17. Nature. 2000 Sep 21;407(6802):390-5 - PubMed
  18. J Biol Chem. 2003 Jul 11;278(28):26046-54 - PubMed
  19. Biochem Pharmacol. 2014 Nov 1;92(1):102-11 - PubMed
  20. J Nutr Biochem. 2014 Jan;25(1):19-25 - PubMed
  21. Gastroenterology. 1998 Nov;115(5):1049-55 - PubMed
  22. Gastroenterol Res Pract. 2013;2013:187070 - PubMed
  23. PLoS One. 2013;8(2):e56153 - PubMed
  24. J Biol Chem. 2001 Apr 13;276(15):12076-83 - PubMed
  25. Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):719-24 - PubMed
  26. Biochem Biophys Res Commun. 2014 Jan 24;443(4):1162-8 - PubMed
  27. J Biol Chem. 2003 Sep 26;278(39):37832-9 - PubMed
  28. Oncotarget. 2014 Feb 15;5(3):716-25 - PubMed
  29. Chem Res Toxicol. 2004 Oct;17(10):1313-22 - PubMed
  30. Biochem Biophys Res Commun. 2014 Apr 4;446(2):541-8 - PubMed
  31. Cancer Sci. 2004 Aug;95(8):644-50 - PubMed
  32. Trends Biochem Sci. 2001 Nov;26(11):657-64 - PubMed
  33. Oncol Lett. 2013 Mar;5(3):975-977 - PubMed
  34. PPAR Res. 2014;2014:215631 - PubMed
  35. Liver Int. 2003 Dec;23(6):460-6 - PubMed
  36. Biochemistry. 2005 Oct 25;44(42):13893-901 - PubMed

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