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 Travers

Research output: Contribution to journalArticle

26 Citations (Scopus)

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

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Chemotherapy
Platelet Activating Factor
Cells
Apoptosis
Carcinoma
Drug Therapy
Cell Line
Oxidative stress
Oxidative Stress
Mitomycin
Etoposide
Cytotoxicity
Ablation
platelet activating factor receptor
Transcription Factors
Tumor Necrosis Factor-alpha
Antioxidants
Ligands
Lipids

ASJC Scopus subject areas

  • Biochemistry

Cite this

The epidermal platelet-activating factor receptor augments chemotherapy-induced apoptosis in human carcinoma cell lines. / Li, Tao; Southall, Michael D.; Yi, Qiaofang; Pei, Yong; Lewis, Davina; Al-Hassani, Mohammed; Spandau, Dan; Travers, Jeffrey.

In: Journal of Biological Chemistry, Vol. 278, No. 19, 09.05.2003, p. 16614-16621.

Research output: Contribution to journalArticle

Li, Tao ; Southall, Michael D. ; Yi, Qiaofang ; Pei, Yong ; Lewis, Davina ; Al-Hassani, Mohammed ; Spandau, Dan ; Travers, Jeffrey. / The epidermal platelet-activating factor receptor augments chemotherapy-induced apoptosis in human carcinoma cell lines. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 19. pp. 16614-16621.
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