Additive effects of C2-ceramide on paclitaxel-induced premature senescence of human lung cancer cells

Jeff Yi Fu Chen, Chi Ching Hwang, Wei Yi Chen, Jing Ching Lee, Tzu Fun Fu, Kang Fang, Ying Chieh Chu, Ya Lan Huang, Jia Cheng Lin, Wen Hui Tsai, Hsueh Wei Chang, Bing Hung Chen, Chien Chih Chiu

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Abstract

Aims: The aims of the study are to investigate the additive effect of exogenous short-carbon chain phospholipids, C2-ceramide, on an anti-cancer drug paclitaxel (PTX)-induced senescence of human non-small cell lung cancer (NSCLC) cells deficient in functional p53 and p16, and to examine whether mitogen-activated protein kinase (MAPK) plays a role in ceramide-sensitized senescence of NSCLC cells. Main methods: To determine whether exogenous C2-ceramide renders lung cancer cells more sensitive to PTX treatment, techniques employing a flow cytometry-based cell cycle analysis and acidic β-galactosidase staining for senescent cells were used. Furthermore, to elucidate the role of MAPK proteins in modulating senescence, assays for protein levels of selective MAPKs and Bcl-2 family members, and detection of transcriptional levels senescence-associated genes were used in the study. Key findings: A sub-lethal dose of C2-ceramide sensitized the NSCLC H1299 cells to PTX treatment. The additive effects of C2-ceramide and PTX resulted in proliferative inhibition, G2-phase arrest of cell cycle, activation of p38 and eventually premature senescence. Importantly, neither p53, p21waf1/cip1 nor p16ink4 was shown to be involved in C2-ceramide-sensitized proliferative inhibition and senescence of H1299 cells by PTX in our study. Significance: Our study demonstrates that the short-carbon chain C2-ceramide can effectively sensitize PTX-induced senescence of H1299 cells via both p21waf1/cip1- and p16ink4-independent pathways.

Original languageEnglish
Pages (from-to)350-357
Number of pages8
JournalLife Sciences
Volume87
Issue number11-12
DOIs
Publication statusPublished - 2010 Sep 1

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Keywords

  • Ceramide
  • P21
  • P38
  • Paclitaxel
  • Senescence

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Chen, J. Y. F., Hwang, C. C., Chen, W. Y., Lee, J. C., Fu, T. F., Fang, K., Chu, Y. C., Huang, Y. L., Lin, J. C., Tsai, W. H., Chang, H. W., Chen, B. H., & Chiu, C. C. (2010). Additive effects of C2-ceramide on paclitaxel-induced premature senescence of human lung cancer cells. Life Sciences, 87(11-12), 350-357. https://doi.org/10.1016/j.lfs.2010.06.017