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Life Sci. 2010 Sep 11;87(11-12):350-7. doi: 10.1016/j.lfs.2010.06.017. Epub 2010 Jul 17.

Additive effects of C(2)-ceramide on paclitaxel-induced premature senescence of human lung cancer cells.

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1
Department of Biotechnology, Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

Abstract

AIMS:

the aims of the study are to investigate the additive effect of exogenous short-carbon chain phospholipids, C(2)-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 C(2)-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 C(2)-ceramide sensitized the NSCLC H1299 cells to PTX treatment. The additive effects of C(2)-ceramide and PTX resulted in proliferative inhibition, G(2)-phase arrest of cell cycle, activation of p38 and eventually premature senescence. Importantly, neither p53, p21(waf1/cip1) nor p16(ink4) was shown to be involved in C(2)-ceramide-sensitized proliferative inhibition and senescence of H1299 cells by PTX in our study.

SIGNIFICANCE:

our study demonstrates that the short-carbon chain C(2)-ceramide can effectively sensitize PTX-induced senescence of H1299 cells via both p21(waf1/cip1)- and p16(ink4)-independent pathways.

PMID:
20624405
DOI:
10.1016/j.lfs.2010.06.017
[Indexed for MEDLINE]

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