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

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

Affiliations

  • 1 Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan. yuli33@ms28.hinet.net.
  • 2 Chest Surgery, Chi-Mei Medical Center, Yung Kang City, Tainan 901, Taiwan. yaou.fong@msa.hinet.net.
  • 3 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. tsaieing@yahoo.com.
  • 4 Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. tsaieing@yahoo.com.
  • 5 Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. yaginchang@hotmail.com.tw.
  • 6 Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. d992050005@student.nsysu.edu.tw.
  • 7 Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. cywu@mail.nsysu.edu.tw.
  • 8 Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan;. cywu@mail.nsysu.edu.tw.
  • 9 Department of Biological Sciences and Technology, National University of Tainan, Tainan 700, Taiwan. tengyenni@mail.nutn.edu.tw.
  • 10 Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan. d730093@cc.kmu.edu.tw.
  • 11 Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. d730093@cc.kmu.edu.tw.
  • 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. yuanssf@ms33.hinet.net.
  • 13 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. cchiu@kmu.edu.tw.
  • 14 Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. cchiu@kmu.edu.tw.
  • 15 Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan;. cchiu@kmu.edu.tw.
  • 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. cchiu@kmu.edu.tw.
  • 17 Research Center for Environment Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. cchiu@kmu.edu.tw.
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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