Abstract 3312: Growth inhibition of cancer cells by 5-aminolevulinic acid

Abstract

Abstract Introduction: 5-aminolevulinic acid (ALA) is intracellularly metabolized to protoporphyrin IX (PpIX) in heme synthetic pathway. As PpIX is a fluorescent photosensitizer and has been shown to accumulate preferentially in cancer cells, exogenously administered ALA is used for photodynamic diagnosis (PDD) and photodynamic therapy (PDT). However, the influence of exogenously administered ALA on cellular proliferation is not elucidated. Overproduction of heme owing to exogenously administered ALA may induce an upregulation of heme oxygenase (HO-1), which is a potential inhibitor of cellular proliferation via a generation of carbon monoxide (CO) and an induction of P21. We therefore examined cytotoxicity when I was administered. Methods and Materials: Human cancer cell lines (10 types) and human normal cell lines (2 types) were incubated with ALA (1.0 mM) for 24 hrs. A fluorometric measurement for PpIX (ex. 405 nm. em. 630 nm) and a proliferation assay using WST-8 were carried out. The expression of HO-1 was evaluated using Western blotting. Results: In 8 out of 10 cancer cell lines, an amount of intracellularly synthesized PpIX after the administration of ALA was highly correlated with a decrease in number of cells (cell death) (R = 0.73), and two out of the eight cell lines (HepG2 and Caki-1) showed a significant reduction in number of cells (> 15%) accompanied with a significant increase in PpIX generation (> 90 a.u.). On the other hand, normal cell lines (HUVEC, SMC) showed less changes in cell count (within 1.5%) accompanied with less PpIX generation (within 35 a.u.). The HO-1 production rate, defined by HO-1 expression level in ALA-treated cells / HO-1 expression level in non-treated cells was highly correlated with the cell death (R = 0.67). Conclusion: In some types of cancer cell lines, an exogenously administered ALA leads to cell death, probably due to the upregulation of HO-1 that is produced by the accumulation of PpIX. Meanwhile, in normal cell lines, the exogenously administered ALA is less likely to induce cell death. Citation Format: Toshikatsu Horiuchi, Yusuke Serizawa, Syoichiro Tateishi, Keiichi Iwaya, Junichi Watanabe, Shinichi Kobayashi, Ken Sato, Fumihiko Kimura, Nariyoshi Shinomiya, Yuji Morimoto. Growth inhibition of cancer cells by 5-aminolevulinic acid. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3312. doi:10.1158/1538-7445.AM2015-3312