Experimental Photodynamic Therapy for Liver Cancer Cell-Implanted Nude Mice by an Indole-3-acetic Acid and Intense Pulsed Light Combination

Abstract

Recently, indole-3-acetic acid (IAA) has been introduced as a new cancer therapeutic agent through oxidative decarboxylation by horseradish peroxidase (HRP). The purpose of this study was to determine the therapeutic feasibility of IAA/light combination against liver cancer. SK-HEP-1 cells were irradiated with UVB or visible light (518 nm) in the presence of IAA. Cell viability was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Then, IAA was injected in SK-HEP-1 liver cancer cell-implanted nude mice, and the tumor area was irradiated with intense pulsed light (IPL). Then, tissue was taken for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay and immunohistochemical staining for 8-hydroxy-deoxyguanosine (8-OHdG), p53, caspase-3, and proliferating cell nuclear antigen (PCNA). In vitro experiments demonstrated that IAA alone was not cytotoxic, but activated IAA by HRP or light caused cell death. In vivo experiments showed that IAA/IPL treatment caused regression of tumor cells in SK-HEP-1-implanted nude mice. The TUNEL assay showed that IAA/IPL induced cancer cell apoptosis, and this was confirmed by increases in 8-OHdG, p53, and caspase-3 in IAA/IPL-treated mice. In contrast, IPL alone did not induce apoptosis, indicating that the apoptotic effect resulted from activated IAA by light. In summary, we showed that IAA/light induced tumor regression in SK-HEP-1-implanted nude mice. These results suggest the potential use of IAA/light combination in liver cancer.