PMID- 34265852
OWN - NLM
STAT- MEDLINE
DCOM- 20220131
LR  - 20220131
IS  - 1349-9157 (Electronic)
IS  - 0449-3060 (Print)
IS  - 0449-3060 (Linking)
VI  - 62
IP  - 5
DP  - 2021 Sep 13
TI  - MHY1485 enhances X-irradiation-induced apoptosis and senescence in tumor cells.
PG  - 782-792
LID - 10.1093/jrr/rrab057 [doi]
AB  - The mammalian target of rapamycin (mTOR) is a sensor of nutrient status and plays 
      an important role in cell growth and metabolism. Although inhibition of mTOR 
      signaling promotes tumor cell death and several mTOR inhibitors have been used 
      clinically, recent reports have shown that co-treatment with MHY1485, an mTOR 
      activator, enhances the anti-cancer effects of anti-PD-1 antibody and 
      5-fluorouracil. However, it remains unclear whether MHY1485 treatment alters the 
      effects of radiation on tumor cells. In this study, the radiosensitizing effects 
      of MHY1485 were investigated using murine CT26 and LLC cell lines. We examined 
      mTOR signaling, tumor cell growth, colony formation, apoptosis, senescence, 
      oxidative stress, p21 accumulation and endoplasmic reticulum (ER) stress levels 
      in cells treated with MHY1485 and radiation, either alone or together. We found 
      that MHY1485 treatment inhibited growth and colony formation in both cell lines 
      under irradiation and no-irradiation conditions, results that were not fully 
      consistent with MHY1485's known role in activating mTOR signaling. Furthermore, 
      we found that combined treatment with MHY1485 and radiation significantly 
      increased apoptosis and senescence in tumor cells in association with oxidative 
      stress, ER stress and p21 stabilization, compared to radiation treatment alone. 
      Our results suggested that MHY1485 enhances the radiosensitivity of tumor cells 
      by a mechanism that may differ from MHY1485's role in mTOR activation.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of The 
      Japanese Radiation Research Society and Japanese Society for Radiation Oncology.
FAU - Sun, Lue
AU  - Sun L
AD  - Health and Medical Research Institute, Department of Life Science and 
      Biotechnology, National Institute of Advanced Industrial Science and Technology 
      (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
FAU - Morikawa, Kumi
AU  - Morikawa K
AD  - Health and Medical Research Institute, Department of Life Science and 
      Biotechnology, National Institute of Advanced Industrial Science and Technology 
      (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
FAU - Sogo, Yu
AU  - Sogo Y
AD  - Health and Medical Research Institute, Department of Life Science and 
      Biotechnology, National Institute of Advanced Industrial Science and Technology 
      (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
FAU - Sugiura, Yuki
AU  - Sugiura Y
AD  - Health and Medical Research Institute, Department of Life Science and 
      Biotechnology, National Institute of Advanced Industrial Science and Technology 
      (AIST), 2217-14, Hayashi-cho, Takamatsu, Kagawa 761-0895, Japan.
LA  - eng
GR  - 19 K22586/Japan Society for the Promotion of Science/
PT  - Journal Article
PL  - England
TA  - J Radiat Res
JT  - Journal of radiation research
JID - 0376611
RN  - 0 (4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine)
RN  - 0 (Morpholines)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Triazines)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects/radiation effects
MH  - Carcinoma, Lewis Lung/genetics/pathology
MH  - Cell Cycle/drug effects/radiation effects
MH  - Cell Line, Tumor
MH  - Cellular Senescence/*drug effects/radiation effects
MH  - Colonic Neoplasms/genetics/pathology
MH  - Drug Screening Assays, Antitumor
MH  - Endoplasmic Reticulum Stress/drug effects/radiation effects
MH  - Genes, p53
MH  - Genes, ras
MH  - Lipid Peroxidation/drug effects/radiation effects
MH  - Mice
MH  - Mitochondria/drug effects/radiation effects
MH  - Morpholines/*pharmacology
MH  - Neoplasm Proteins/*agonists/biosynthesis/genetics
MH  - Signal Transduction/drug effects/radiation effects
MH  - TOR Serine-Threonine Kinases/*drug effects
MH  - Triazines/*pharmacology
MH  - Tumor Stem Cell Assay
PMC - PMC8438247
OTO - NOTNLM
OT  - MHY1485
OT  - apoptosis
OT  - mammalian target of rapamycin (mTOR)
OT  - radiation
OT  - senescence
EDAT- 2021/07/16 06:00
MHDA- 2022/02/01 06:00
PMCR- 2021/07/16
CRDT- 2021/07/15 20:36
PHST- 2021/02/24 00:00 [received]
PHST- 2021/05/27 00:00 [revised]
PHST- 2021/07/16 06:00 [pubmed]
PHST- 2022/02/01 06:00 [medline]
PHST- 2021/07/15 20:36 [entrez]
PHST- 2021/07/16 00:00 [pmc-release]
AID - 6322308 [pii]
AID - rrab057 [pii]
AID - 10.1093/jrr/rrab057 [doi]
PST - ppublish
SO  - J Radiat Res. 2021 Sep 13;62(5):782-792. doi: 10.1093/jrr/rrab057.