Tuesday, 15 May 2018: 11:40
Room 204 (Washington State Convention Center)
Photodynamic therapy is useful for the treatment of cancer because it is minimally invasive for patients. Certain porphyrin compounds and their derivatives have been used as the photosensitizer because they accumulate specifically in cancerous tissues. However, the detailed mechanism of this phenomenon has not been clarified. We previously reported that a proton-coupled folate transporter, HCP1, transported porphyrins and that regulation of the protein was associated with cancer-specific reactive oxygen species from mitochondria (mitROS) (Hiyama K et al. J PorphPhtal. 2013; 17: 36–43). Therefore, over-generation of mitROS could increase HCP1 expression and the effect of photodynamic therapy. We investigated whether pretreatment with indomethacin influenced photodynamic therapy by using a rat normal gastric mucosal cell line, RGM1, its cancer-like mutated cell line, RGK1, and a manganese superoxide dismutase (MnSOD)-overexpressed RGK cell line, RGK-MnSOD. Indomethacin promotes the generation of cellular mitROS by inhibiting the electron transport chain, and MnSOD scavenges the mitROS. We elucidated that hyperthemia enhanced cancer-specific mitROS generation and increased HCP1 expression. Furthermore, RGK1 cells showed higher cellular incorporation of hemato-porphyrin and better therapeutic effect with indomethacin treatment whereas RGK-MnSOD cells did not show a difference. Thus, we concluded that hyperthermia improved the effect of photodynamic therapy by inducing increased mitROS generation in cancer cells.
References
1. Ito, H., H. Matsui, A. Hirayama, H. P. Indo, H. J. Majima and I. Hyodo (2016) Reactive oxygen species induced by non-steroidal anti-inflammatory drugs enhance the effects of photodynamic therapy in gastric cancer cells. Journal of clinical biochemistry and nutrition 58, 180-185.
2. Ito, H., M. Tamura, H. Matsui, H. J. Majima, H. P. Indo and I. Hyodo (2014) Reactive oxygen species involved cancer cellular specific 5-aminolevulinic acid uptake in gastric epithelial cells. Journal of clinical biochemistry and nutrition 54, 81-85.
3. Ito, H., H. Matsui, M. Tamura, H. J. Majima, H. P. Indo and I. Hyodo (2014) Mitochondrial reactive oxygen species accelerate the expression of heme carrier protein 1 and enhance photodynamic cancer therapy effect. Journal of clinical biochemistry and nutrition 55, 67-71.
References
1. Ito, H., H. Matsui, A. Hirayama, H. P. Indo, H. J. Majima and I. Hyodo (2016) Reactive oxygen species induced by non-steroidal anti-inflammatory drugs enhance the effects of photodynamic therapy in gastric cancer cells. Journal of clinical biochemistry and nutrition 58, 180-185.
2. Ito, H., M. Tamura, H. Matsui, H. J. Majima, H. P. Indo and I. Hyodo (2014) Reactive oxygen species involved cancer cellular specific 5-aminolevulinic acid uptake in gastric epithelial cells. Journal of clinical biochemistry and nutrition 54, 81-85.
3. Ito, H., H. Matsui, M. Tamura, H. J. Majima, H. P. Indo and I. Hyodo (2014) Mitochondrial reactive oxygen species accelerate the expression of heme carrier protein 1 and enhance photodynamic cancer therapy effect. Journal of clinical biochemistry and nutrition 55, 67-71.