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Hokkaido University Collection of Scholarly and Academic Papers >
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LAT1 inhibitor JPH203 sensitizes cancer cells to radiation by enhancing radiation-induced cellular senescence
| Title: | LAT1 inhibitor JPH203 sensitizes cancer cells to radiation by enhancing radiation-induced cellular senescence |
| Authors: | Bo, Tomoki Browse this author | | Kobayashi, Sho Browse this author | | Inanami, Osamu Browse this author →KAKEN DB | | Fujii, Junichi Browse this author | | Nakajima, Osamu Browse this author | | Ito, Tsunekata Browse this author | | Yasui, Hironobu Browse this author →KAKEN DB |
| Keywords: | Cancer metabolism | | JPH203 | | LAT1 | | Neutral amino acids | | Radiation |
| Issue Date: | Nov-2021 |
| Publisher: | Elsevier |
| Journal Title: | Translational Oncology |
| Volume: | 14 |
| Issue: | 11 |
| Start Page: | 101212 |
| Publisher DOI: | 10.1016/j.tranon.2021.101212 |
| Abstract: | L-type amino acid transporter 1 (LAT1) is important for transporting neutral amino acids into cells. LAT1 expression is correlated with cancer malignancy, suggesting that LAT1 is a promising target for cancer therapy. JPH203, a potential novel drug targeting LAT1, has been shown to suppress tumor growth in various cancer cell lines. However, a combination study of JPH203 and radiation therapy has not been reported. Here, we examined the effects of JPH203 on radiosensitivity after irradiation in A549 and MIA Paca-2 cells. We showed that X irradiation increased cellular neutral amino acid uptake via LAT1 in both cell lines. JPH203 inhibited the radiation-induced increase in neutral amino acid uptake. We demonstrated that JPH203, at minimally toxic concentrations, significantly sensitized cancer cells to radiation. JPH203 significantly downregulated mTOR activity and enhanced cellular senescence post-irradiation without reducing ATP and GSH levels. These results indicate that LAT1 inhibition by JPH203 sensitizes cancer cells to radiation by enhancing cellular senescence via mTOR downregulation. Thus, JPH203 may be a potent anti-cancer drug in combination with radiation therapy. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/83493 |
| Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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