RT Journal Article
SR Electronic
T1 Synergistic Effects of Melatonin on Radiosensitization in Carbon-ion Radiotherapy
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3295
OP 3306
DO 10.21873/anticanres.17148
VO 44
IS 8
A1 JU, MENGYANG
A1 MINAMI, KAZUMASA
A1 KATSUKI, SHOHEI
A1 TAKENAKA, WATARU
A1 TATEKAWA, SHOTARO
A1 TAMARI, KEISUKE
A1 KOIZUMI, MASAHIKO
A1 TAKAHASHI, YUTAKA
A1 OGAWA, KAZUHIKO
YR 2024
UL http://ar.iiarjournals.org/content/44/8/3295.abstract
AB Background/Aim: Despite the established antitumor effectiveness and synergistic interactions of melatonin with photon irradiation, its role in carbon-ion radiotherapy remains uncertain. This study aimed to elucidate the mechanisms and potential clinical advantages of combining exogenous melatonin therapy with carbon-ion radiotherapy. Materials and Methods: The investigation assessed the impact of combining exogenous melatonin with photon or carbon-ion irradiation on cell-cycle modulation and DNA-repair capability using the melanoma cell line B16F10. RNA sequencing and bioinformatics analysis were conducted to explore mechanisms and evaluate potential clinical benefits, with validation performed on the osteosarcoma cell line LM8. Results: Pre-treatment with melatonin reduced the survival fraction of B16F10 and LM8 cells upon exposure to photon and carbon-ion radiation. Mechanistically, melatonin was found to inhibit G2/M arrest, preserve DNA damage, and suppress key genes involved in DNA double-strand break repair after 8 Gy carbon-ion radiation. Furthermore, RNA sequencing and bioinformatics analysis revealed favorable changes in genes associated with survival and metastasis, highlighting potential clinical significance. LM8 cells treated with melatonin exhibited increased radiosensitivity and suppression of DNA-repair proteins. Conclusion: The combination of exogenous melatonin not only heightened radiosensitivity and modulated hallmark tumor gene sets in vitro but also markedly suppressed the efficiency of DNA double-strand break-repair pathway, thus enhancing the cytotoxicity of carbon-ion radiotherapy.