The epidermal platelet-activating factor receptor augments chemotherapy-induced apoptosis in human carcinoma cell lines

Tao Li, Michael D. Southall, Qiaofang Yi, Yong Pei, Davina Lewis, Mohammed Al-Hassani, Dan Spandau, Jeffrey B. Travers

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Most chemotherapeutic agents exert their cytotoxic effects in part through the induction of apoptosis. In addition, many chemotherapeutic agents are potent pro-oxidative stressors. Although the lipid mediator platelet-activating factor (PAF) is synthesized in response to oxidative stress, and many epidermal carcinomas express PAF receptors, it is not known whether PAF is involved in chemotherapeutic agent-induced apoptosis. These studies examined the role of the PAF system in chemotherapy-mediated cytotoxicity using model systems created by retroviral mediated transduction of the PAF receptor-negative human epidermal carcinoma cell line KB with the human PAF receptor (PAF-R) and ablation of the endogenous PAF-R in the carcinoma cell line HaCaT with a retroviral mediated inducible antisense PAF-R vector. The presence of the PAF-R in these models resulted in an augmentation of apoptosis induced by chemotherapeutic agents etoposide and mitomycin C but not by tumor necrosis factor-related apoptosis-inducing ligand or by C2 ceramide. Oxidative stress and the transcription factor nuclear factor κB (NF-κB) are found to be involved in this augmentative effect because it was blocked by antioxidants and inhibition of the NF-κB pathway using a super-repressor form of inhibitor B. These studies provide evidence for a novel pathway whereby the epidermal PAF-R can augment chemotherapy-induced apoptotic effects through an NF-κB-dependent process.

Original languageEnglish (US)
Pages (from-to)16614-16621
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number19
DOIs
StatePublished - May 9 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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