Enhanced radiosensitization of p53 mutant cells by oleamide

Yoon Jin Lee, Da Yeon Chung, Su Jae Lee, Gil Ja Jhon, Yun Sil Lee

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Purpose: Effect of oleamide, an endogenous fatty-acid primary amide, on tumor cells exposed to ionizing radiation (IR) has never before been explored. Methods and Materials: NCI H460, human lung cancer cells, and human astrocytoma cell lines, U87 and U251, were used. The cytotoxicity of oleamide alone or in combination with IR was determined by clonogenic survival assay, and induction of apoptosis was estimated by FACS analysis. Protein expressions were confirmed by Western blotting, and immunofluorescence analysis of Bax by use of confocal microscopy was also performed. The combined effect of IR and oleamide to suppress tumor growth was studied by use of xenografts in the thighs of nude mice. Results: Oleamide in combination with IR had a synergistic effect that decreased clonogenic survival of lung-carcinoma cell lines and also sensitized xenografts in nude mice. Enhanced induction of apoptosis of the cells by the combined treatment was mediated by loss of mitochondrial membrane potential, which resulted in the activation of caspase-8, caspase-9, and caspase-3 accompanied by cytochrome c release and Bid cleavage. The synergistic effects of the combined treatment were more enhanced in p53 mutant cells than in p53 wild-type cells. In p53 wild-type cells, both oleamide and radiation induced Bax translocation to mitochondria. On the other hand, in p53 mutant cells, radiation alone slightly induced Bax translocation to mitochondria, whereas oleamide induced a larger translocation. Conclusions: Oleamide may exhibit synergistic radiosensitization in p53 mutant cells through p53-independent Bax translocation to mitochondria.

Original languageEnglish
Pages (from-to)1466-1474
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number5
StatePublished - 1 Apr 2006

Bibliographical note

Funding Information:
This study was supported by Health Technology Planning & Evaluation Board, Korean government through its IMT2000 Program (2002–2004).


  • Bax translocation
  • Oleamide
  • p53 mutant cells
  • Radiosensitization


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