Spatiotemporal metabolic dynamics of the photosensitizer talaporfin sodium in carcinoma and sarcoma.

Affiliation

Saito T(1)(2), Tsukahara T(1), Suzuki T(3), Nojima I(4), Tadano H(1)(5), Kawai N(1)(6), Kubo T(1), Hirohashi Y(1), Kanaseki T(1), Torigoe T(1), Li L(2).
Author information:
(1)Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
(2)Graduate School of Photonic Science, Chitose Institute for Science and Technology, Sapporo, Japan.
(3)Department of Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
(4)Division of Cell Bank, Biomedical Research, Education and Instrumentation Center, Sapporo Medical University School of Medicine, Sapporo, Japan.
(5)Division of Internal Medicine, Sapporo Self-Defense Forces Hospital, Sapporo, Japan.
(6)Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Abstract

Photodynamic therapy (PDT) using the photosensitizer talaporfin sodium (talaporfin) is a new mode of treatment for cancer. However, the metabolic mechanism of talaporfin has not been clarified. Thus, we investigated the uptake, transportation, and elimination mechanisms of talaporfin in carcinoma and sarcoma. The results showed that talaporfin co-localized in early endosomes and lysosomes. Talaporfin uptake was via clathrin- and caveolae-dependent endocytosis and a high amount of intracellular ATP was essential. Inhibition of lysosomal enzymes maintained intracellular talaporfin levels. Inhibition of K-Ras signaling reduced talaporfin uptake in carcinoma and sarcoma cell lines. Talaporfin was taken up by clathrin- and caveolae-dependent endocytosis, translocated from early endosomes to lysosomes, and finally degraded by lysosomes. We also demonstrated that ATP is essential for the uptake of talaporfin and that activation of K-Ras is involved as a regulatory mechanism. These results provide new insights into the metabolism of talaporfin in cancer cells for the enhancement of PDT for carcinoma and sarcoma.