Mechanism of Differential Susceptibility of Two (Canine Lung Adenocarcinoma) Cell Lines to 5-Aminolevulinic Acid-Mediated Photodynamic Therapy

  • Cancers (Basel). 2021 Aug 19;13(16):4174. doi: 10.3390/cancers13164174.
Tomohiro Osaki  1 Narumi Kunisue  2 Urara Ota  2 Hideo Imazato  2 Takuya Ishii  2 Kiwamu Takahashi  2 Masahiro Ishizuka  2 Tohru Tanaka  3 Yoshiharu Okamoto  1
Affiliations
  • 1. Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan.
  • 2. SBI Pharmaceuticals Co., Ltd., Tokyo 106-6020, Japan.
  • 3. Neopharma Japan Co., Ltd., Tokyo 102-0071, Japan.
Abstract

Photodynamic therapy (PDT) is a clinically approved, minimally invasive treatment for malignant tumors. Protoporphyrin IX (PpIX), derived from 5-aminolevulinic acid (5-ALA) as the prodrug, is one of the photosensitizers used in PDT. Recently, we reported a significant difference in response to 5-ALA-mediated PDT treatment in two canine primary lung adenocarcinoma cell lines (sensitive to PDT: HDC cells, resistant to PDT: LuBi cells). This study aimed to examine the difference in cytotoxicity of 5-ALA-mediated PDT in these cells. Although intracellular PpIX levels before irradiation were similar between HDC and LuBi cells, the percentage of ROS-positive cells and apoptotic cells in LuBi cells treated with 5-ALA-mediated PDT was significantly lower than that in HDC cells treated with 5-ALA-mediated PDT. A high dosage of the NO donor, DETA NONOate, significantly increased the cytotoxicity of 5-ALA-mediated PDT against LuBi cells. These results suggest that the sensitivity of 5-ALA-mediated PDT might be correlated with NO.

Keywords
canine carcinoma; lung adenocarcinoma; photodynamic therapy; tumor.
Products