Abstract 4903: Luteolin's role as a radiosensitizer by promoting cell death and ROS modulation

Abstract

Abstract Radiotherapy is one of major cancer treatment, but radiation treatment could evoke resistance or side effects such as fibrosis. To overcome these obstacles against radiation treatment, many researchers are developing effective radiosensitizer. To develop a new radiosensitizer, we test whether luteolin has functions as a radiosensitizer candidate because previous studies already demonstrated luteolin could promote cancer cell death by reactive oxygen species (ROS) induction, and this phenomenon is one of main effects of radiation-induced cell death. Luteolin is 3′,4′,5,7-tetrahydroxyflavone, which could induce cell death of various cancer cells. We observed luteolin treatment could induce cell death of non-small cell lung cancer cells with independent manner of p53 and PTEN status, and combination treatment of radiation and luteolin enhance more cell death than those of radiation only or luteolin only treatment condition. Dose enhancement ratios of luteolin and radiation combination are 1.54 and 1.31 in NCI-H460 and NCI-H1299, respectively. Combined treatment with luteolin and radiation down-regulate Bcl-2 level and induce the phosphorylation of JNK and activation of caspase-3/9. ROS accumulation also was induced in combined condition of luteolin and radiations. In a xenograft assay, the combined luteolin and radiation group showed 27.2 days of growth delay versus the control in terms of tumor growth. The enhancement factor of this combined treatment was determined to be 3.2. Taken together, we conclude that luteolin contain role of radiosensitizer via promotion of cell death and ROS accumulation. Citation Format: Kwang-Chul Ahn, Jae Yeon Choi, Sang-Gu Hwang, Hong-Duck Um, Jong Kuk Park. Luteolin's role as a radiosensitizer by promoting cell death and ROS modulation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4903. doi:10.1158/1538-7445.AM2014-4903