Enhancement of radiosensitivity by combined ceramide and dimethylsphingosine treatment in lung cancer cells

Hye Won Park, Jie Young Song, Ki Sung Kim, Youngsoo Han, Chan Wha Kim, Seh Yoon Yi, Yeon Sook Yun

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Ceramide generated from sphingomyelin in response to ionizing radiation has been implicated as a second messenger to induce cellular proapoptotic signals. Both ceramide and its metabolic inhibitor, N, N-dimethyl-D-erythro-sphingosine (DMS), might lead to sustained ceramide accumulation in cells more efficiently, thereby sensitizing them to γ-radiation-induced cell death. To delineate this problem, the clonogenic survival of Lewis lung carcinoma (LLC) cells was evaluated following exposure to radiation together with or without C2-ceramide, DMS, or both. The treatment of ceramide/DMS synergistically decreased the survival of the irradiated cells compared with treatment with ceramide or DMS alone. Ceramide/DMS-treated cells displayed several apoptotic features after γ-irradiation, including increased sub G1 population, TUNEL-positive fraction, and poly-(ADP-ribose) polymerase (PARP) cleavage. We also observed ceramide/DMS induced disruption of mitochondrial membrane potential (MMP) and activation of caspase-9 and -3 in a radiation-dose-dependent manner. Furthermore, pretreatment of LLC cells with ceramide/DMS not only increased the protein expression level of Bax, but also decreased Bcl-2 after γ-irradiation. Taken together, the present study indicates that the radiosensitizing activity of ceramide/DMS on LLC cells most likely reflects the dominance of pro-apoptotic signals related to the mitochondria-dependent pathway.

Original languageEnglish
Pages (from-to)411-419
Number of pages9
JournalExperimental and Molecular Medicine
Volume36
Issue number5
DOIs
Publication statusPublished - 2004 Oct 31

Keywords

  • Apoptosis
  • Ceramide
  • DMS
  • Radiosensitivity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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