PMID- 34329824
OWN - NLM
STAT- MEDLINE
DCOM- 20220106
LR  - 20220106
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 142
DP  - 2021 Oct
TI  - Improved tumor-suppressive effect of OZ-001 combined with cisplatin mediated by 
      mTOR/p70S6K and STAT3 inactivation in A549 human lung cancer cells.
PG  - 111961
LID - S0753-3322(21)00743-5 [pii]
LID - 10.1016/j.biopha.2021.111961 [doi]
AB  - We previously reported the anticancer activity of 
      4-(4-fluorobenzylcarbamoylmethyl)-3-(4-cyclohexylphenyl)-2-[3-(N,N-dimethylureido)-N'-methylpropylamino]-3,4-dihydroquinazoline 
      (OZ-001), a T-type calcium channel (TTCC) blocker, against non-small cell lung 
      cancer (NSCLC) in vitro and in vivo. Here, we evaluated the synergistic effect of 
      OZ-001 and cisplatin on A549 human lung cancer cells and A549 xenograft mice. Our 
      study demonstrated that treatment with OZ-001 and cisplatin sensitized A549 cells 
      to cisplatin and significantly inhibited cell growth, increased the number of 
      terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive 
      cells, and induced poly (ADP-ribose) polymerase (PARP) cleavage in A549 cells and 
      an A549 xenograft tumor mouse model. Moreover, our findings showed that 
      mechanistic target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and 
      signal transducer and activator of transcription (STAT3) inactivation was 
      required for apoptosis induced by the combination of OZ-001 and cisplatin in in 
      vitro and in vivo experiments. Our results suggest that combined treatment with 
      OZ-001 and cisplatin could potentiate antiproliferative effects via suppression 
      of the mTOR/p70S6K and STAT3 pathways and may be considered a potential 
      therapeutic agent for NSCLC.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Lee, Jeong-Hun
AU  - Lee JH
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee 
      University, 26, Kyungheedae-ro, Seoul 02447, Republic of Korea; Department of 
      Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26, 
      Kyungheedae-ro, Seoul 02447, Republic of Korea.
FAU - Chung, Kyung-Sook
AU  - Chung KS
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee 
      University, 26, Kyungheedae-ro, Seoul 02447, Republic of Korea.
FAU - Lee, Hwi-Ho
AU  - Lee HH
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee 
      University, 26, Kyungheedae-ro, Seoul 02447, Republic of Korea.
FAU - Ko, Dohyeong
AU  - Ko D
AD  - Research Institute for Basic Sciences and Department of Chemistry, College of 
      Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.
FAU - Kang, Minji
AU  - Kang M
AD  - Research Institute for Basic Sciences and Department of Chemistry, College of 
      Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.
FAU - Yoo, Ho
AU  - Yoo H
AD  - ONCOZEN Co., Ltd., ONCOZEN R&D Center, C-713, Beobwon-ro 11-gil, Songpa-gu, Seoul 
      05836, Republic of Korea.
FAU - Ahn, JooHoon
AU  - Ahn J
AD  - ONCOZEN Co., Ltd., ONCOZEN R&D Center, C-713, Beobwon-ro 11-gil, Songpa-gu, Seoul 
      05836, Republic of Korea.
FAU - Lee, Jae Yeol
AU  - Lee JY
AD  - Research Institute for Basic Sciences and Department of Chemistry, College of 
      Sciences, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic 
      address: ljy@khu.ac.k.
FAU - Lee, Kyung-Tae
AU  - Lee KT
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee 
      University, 26, Kyungheedae-ro, Seoul 02447, Republic of Korea; Department of 
      Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26, 
      Kyungheedae-ro, Seoul 02447, Republic of Korea. Electronic address: 
      ktlee@khu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20210728
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - A549 Cells
MH  - Animals
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & 
      dosage/*pharmacology
MH  - Cisplatin/administration & dosage/*pharmacology
MH  - Drug Synergism
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Lung Neoplasms/*drug therapy
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - Apoptosis
OT  - Combined therapy
OT  - Non-small cell lung cancer
OT  - OZ-001
OT  - P70S6K
EDAT- 2021/07/31 06:00
MHDA- 2022/01/07 06:00
CRDT- 2021/07/30 20:14
PHST- 2021/04/02 00:00 [received]
PHST- 2021/07/16 00:00 [revised]
PHST- 2021/07/22 00:00 [accepted]
PHST- 2021/07/31 06:00 [pubmed]
PHST- 2022/01/07 06:00 [medline]
PHST- 2021/07/30 20:14 [entrez]
AID - S0753-3322(21)00743-5 [pii]
AID - 10.1016/j.biopha.2021.111961 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2021 Oct;142:111961. doi: 10.1016/j.biopha.2021.111961. Epub 
      2021 Jul 28.