Key transporters leading to specific protoporphyrin IX accumulation in cancer cell following administration of aminolevu
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INVITED REVIEW ARTICLE
Key transporters leading to specific protoporphyrin IX accumulation in cancer cell following administration of aminolevulinic acid in photodynamic therapy/diagnosis Hung Wei Lai1 · Taku Nakayama1,2 · Shun‑ichiro Ogura1,2 Received: 30 July 2020 / Accepted: 5 August 2020 © Japan Society of Clinical Oncology 2020
Abstract The administration of aminolevulinic acid allow the formation and accumulation of protoporphyrin IX specifically in cancer cells, which then lead to photocytotoxicity following light irradiation. This compound, when accumulated at high levels, could also be used in cancer diagnosis as it would emit red fluorescence when being light irradiated. The concentration of protoporphyrin IX is pivotal in ensuring the effectiveness of the therapy. Studies have been carried out and showed the importance of various transporters in regulating the amount of these substrates by controlling the transport of various related metabolites in and out of the cell. There are many transporters involved and their expression levels are dependent on various factors, such as oxygen availability and iron ions. It is also important to note that these transporters may also have different expression levels depending on their organ. Understanding the mechanisms and the roles of these transporters are essential to ensure maximum accumulation of protoporphyrin IX, leading to higher efficiency in photodynamic therapy/diagnosis. In this review, we would like to discuss the roles of various transporters in protoporphyrin IX accumulation and how their involvement directly affect cancerous microenvironment. Keywords Aminolevulinic acid · Transporters · Photodynamic therapy · Photodynamic diagnosis · Protoporphyrin IX
Introduction The concept of photodynamic therapy has come a long way ever since its accidental discovery by Oscar Raab in 1900 [1]. Initially being used as an antibacterial treatment, PDT has been incorporated as part of the anti-cancer treatment since the past few decades [2, 3]. Despite that, there are still many questions surrounding the actual mechanism of PpIX accumulation. Photodynamic therapy requires the administration of a photosensitizer, which may be excited by a photon of light at specific wavelength, leading to the initiation of cell-killing action on the target cells [4]. Amongst the various type of * Shun‑ichiro Ogura [email protected] 1
School of Life Science and Technology, Tokyo Institute of Technology, 4259 B47, Nagatsuta‑cho, Midori‑ku, Yokohama 226‑8501, Japan
Center for Photodynamic Medicine, Kochi Medical School, Kohasu, Oko‑cho, Nankoku‑shi, Kochi 783‑8505, Japan
2
photosensitizers, aminolevulinic acid (ALA) is one of the widely studied substances and is gaining popularity in cancer treatment [6]. This is due to its high efficiency against cancer cells and low side effect nature [5, 6]. Differ from other photosensitizers, it is important to note that ALA merely act as a prodrug during its initial stage of exogenous administration, ALA only start to act as an a
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