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

Life Sciences
Jeff Yi-Fu ChenChien-Chih Chiu

Abstract

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. 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. 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 proliferat...Continue Reading

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Citations

Sep 13, 2011·Acta Pharmacologica Sinica·Yi Zhang, Jin-ming Yang
Nov 26, 2013·Mechanisms of Ageing and Development·Kavita S JadhavDavid L Williamson
Jan 5, 2014·Biochimica Et Biophysica Acta·Jean-Philip TrumanYusuf A Hannun
Feb 24, 2015·Apoptosis : an International Journal on Programmed Cell Death·Sehamuddin GaladariFaisal Thayyullathil
Feb 27, 2015·Biological Chemistry·Carla HajjAdriana Haimovitz-Friedman
Dec 9, 2020·Cellular Signalling·Fabiola N VelazquezAshley J Snider

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