Exogenous C₈-Ceramide Induces Apoptosis by Overproduction of ROS and the Switch of Superoxide Dismutases SOD1 to SOD2 in Human Lung Cancer Cells

  • Int J Mol Sci. 2018 Oct 2;19(10):3010. doi: 10.3390/ijms19103010.
Yuli C Chang  1 ,  Yao Fong  2 ,  Eing-Mei Tsai  3  4 ,  Ya-Gin Chang  5 ,  Han Lin Chou  6 ,  Chang-Yi Wu  7  8 ,  Yen-Ni Teng  9 ,  Ta-Chih Liu  10  11 ,  Shyng-Shiou Yuan  12 ,  Chien-Chih Chiu  13  14  15  16  17
Affiliations
  • 1. Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan. [email protected].
  • 2. Chest Surgery, Chi-Mei Medical Center, Yung Kang City, Tainan 901, Taiwan. [email protected].
  • 3. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. [email protected].
  • 4. Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. [email protected].
  • 5. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. [email protected].
  • 6. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. [email protected].
  • 7. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. [email protected].
  • 8. Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan;. [email protected].
  • 9. Department of Biological Sciences and Technology, National University of Tainan, Tainan 700, Taiwan. [email protected].
  • 10. Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan. [email protected].
  • 11. Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. [email protected].
  • 12. Translational Research Center, Cancer Center, Department of Medical Research, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan. [email protected].
  • 13. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. [email protected].
  • 14. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. [email protected].
  • 15. Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan;. [email protected].
  • 16. Translational Research Center, Cancer Center, Department of Medical Research, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan. [email protected].
  • 17. Research Center for Environment Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. [email protected].
PMID: 30279365 DOI: 10.3390/ijms19103010
Abstract

Ceramides, abundant sphingolipids on the cell membrane, can act as signaling molecules to regulate cellular functions including cell viability. Exogenous ceramide has been shown to exert potent anti-proliferative effects against Cancer cells, but little is known about how it affects Reactive Oxygen Species (ROS) in lung Cancer cells. In this study, we investigated the effect of N-octanoyl-D-erythro-sphingosine (C₈-ceramide) on human non-small-cell lung Cancer H1299 cells. Flow cytometry-based assays indicated that C₈-ceramide increased the level of endogenous ROS in H1299 cells. Interestingly, the ratio of superoxide dismutases (SODs) SOD1 and SOD2 seem to be regulated by C₈-ceramide treatment. Furthermore, the accumulation of cell cycle G1 phase and apoptotic populations in C₈-ceramide-treated H1299 cells was observed. The results of the Western blot showed that C₈-ceramide causes a dramatically increased protein level of cyclin D1, a critical regulator of cell cycle G1/S transition. These results suggest that C₈-ceramide acts as a potent chemotherapeutic agent and may increase the endogenous ROS level by regulating the switch of SOD1 and SOD2, causing the anti-proliferation, and consequently triggering the Apoptosis of NSCLC H1299 cells. Accordingly, our works may give a promising strategy for lung Cancer treatment in the future.

Keywords
C8-ceramide; ROS; SOD switch; apoptosis; cyclin D1; lung cancer.
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