PMID- 35525902
OWN - NLM
STAT- MEDLINE
DCOM- 20220510
LR  - 20220716
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 12
IP  - 1
DP  - 2022 May 7
TI  - Oxime derivative TFOBO promotes cell death by modulating reactive oxygen species 
      and regulating NADPH oxidase activity in myeloid leukemia.
PG  - 7519
LID - 10.1038/s41598-022-11543-8 [doi]
LID - 7519
AB  - Several derivatives derived from the oxime structure have been reported as 
      potential anticancer agents in various cancers. Here, we first tested a novel 
      oxime-containing derivative of 2-((2,4,5-trifluorobenzyl)oxy)benzaldehyde oxime 
      (TFOBO) to evaluate its anticancer effect in myeloid leukemic cells. Compared to 
      (2-((2,4,5-trifluorobenzyl)oxy)phenyl)methanol (TFOPM), the oxime derivative 
      TFOBO suppresses leukemic cell growth by significantly increasing reactive oxygen 
      species (ROS) levels and cell death. Leukemic cells treated with TFOBO displayed 
      apoptotic cell death, as indicated by nuclear condensation, DNA fragmentation, 
      and annexin V staining. TFOBO increases Bax/Bcl2 levels, caspase9, and caspase3/7 
      activity and decreases mitochondrial membrane potential. ROS production was 
      reduced by N-acetyl-L-cysteine, a ROS scavenger, diphenyleneiodonium chloride, a 
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, after 
      exogenous TFOBO treatment. ROS inhibitors protect leukemic cells from 
      TFOBO-induced cell death. Thus, our study findings suggest that TFOBO promotes 
      apoptosis by modulating ROS and regulating NADPH oxidase activity. Collectively, 
      the oxime-containing derivative TFOBO is a novel therapeutic drug for myeloid 
      leukemia.
CI  - (c) 2022. The Author(s).
FAU - Jo, Ahyoung
AU  - Jo A
AD  - Department of Pharmacology, School of Medicine, Pusan National University, 
      Yangsan, 50612, Republic of Korea.
FAU - Kwak, Jae-Hwan
AU  - Kwak JH
AD  - College of Pharmacy, Kyungsung University, Busan, 48434, Republic of Korea.
FAU - Woo, Soo-Yeon
AU  - Woo SY
AD  - Department of Convergence Medicine, School of Medicine, Pusan National 
      University, Yangsan, 50612, Republic of Korea.
FAU - Kim, Bo-Young
AU  - Kim BY
AD  - Department of Pharmacology, School of Medicine, Pusan National University, 
      Yangsan, 50612, Republic of Korea.
FAU - Son, Yonghae
AU  - Son Y
AD  - Department of Pharmacology, School of Medicine, Pusan National University, 
      Yangsan, 50612, Republic of Korea.
FAU - Choi, Hee-Seon
AU  - Choi HS
AD  - Department of Convergence Medicine, School of Medicine, Pusan National 
      University, Yangsan, 50612, Republic of Korea.
FAU - Kim, Jayoung
AU  - Kim J
AD  - Department of Convergence Medicine, School of Medicine, Pusan National 
      University, Yangsan, 50612, Republic of Korea.
FAU - Kwon, Munju
AU  - Kwon M
AD  - Department of Convergence Medicine, School of Medicine, Pusan National 
      University, Yangsan, 50612, Republic of Korea.
FAU - Cho, Hyok-Rae
AU  - Cho HR
AD  - Department of Neurosurgery, College of Medicine, Kosin University, Busan, 49267, 
      Republic of Korea.
FAU - Eo, Seong-Kug
AU  - Eo SK
AD  - College of Veterinary Medicine and Bio-Safety Research Institute, Jeonbuk 
      National University, Iksan, 54596, Republic of Korea.
FAU - Nam, Ji Ho
AU  - Nam JH
AD  - Department of Radiation Oncology, Pusan National University School of Medicine, 
      Yangsan, 50612, Republic of Korea.
FAU - Kim, Hyung-Sik
AU  - Kim HS
AD  - Department of Life Science in Dentistry, School of Dentistry, Pusan National 
      University, Yangsan, 50612, Republic of Korea.
FAU - Baryawno, Ninib
AU  - Baryawno N
AD  - Childhood Cancer Research Unit, Department of Women's and Children's Health, 
      Karolinska Institutet, 17177, Stockholm, Sweden. n.baryawno@ki.se.
FAU - Lee, Dongjun
AU  - Lee D
AD  - Department of Convergence Medicine, School of Medicine, Pusan National 
      University, Yangsan, 50612, Republic of Korea. lee.dongjun@pusan.ac.kr.
FAU - Kim, Koanhoi
AU  - Kim K
AD  - Department of Pharmacology, School of Medicine, Pusan National University, 
      Yangsan, 50612, Republic of Korea. koanhoi@pusan.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220507
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Oximes)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Apoptosis
MH  - Cell Death
MH  - Humans
MH  - *Leukemia, Myeloid/drug therapy
MH  - NADPH Oxidases/metabolism
MH  - *Oximes/pharmacology
MH  - Reactive Oxygen Species/metabolism
PMC - PMC9079095
COIS- The authors declare no competing interests.
EDAT- 2022/05/08 06:00
MHDA- 2022/05/11 06:00
PMCR- 2022/05/07
CRDT- 2022/05/07 23:17
PHST- 2022/02/10 00:00 [received]
PHST- 2022/04/18 00:00 [accepted]
PHST- 2022/05/07 23:17 [entrez]
PHST- 2022/05/08 06:00 [pubmed]
PHST- 2022/05/11 06:00 [medline]
PHST- 2022/05/07 00:00 [pmc-release]
AID - 10.1038/s41598-022-11543-8 [pii]
AID - 11543 [pii]
AID - 10.1038/s41598-022-11543-8 [doi]
PST - epublish
SO  - Sci Rep. 2022 May 7;12(1):7519. doi: 10.1038/s41598-022-11543-8.