PMID- 35626090
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 10
DP  - 2022 May 18
TI  - Diphenyleneiodonium Triggers Cell Death of Acute Myeloid Leukemia Cells by 
      Blocking the Mitochondrial Respiratory Chain, and Synergizes with Cytarabine.
LID - 10.3390/cancers14102485 [doi]
LID - 2485
AB  - Acute myeloid leukemia (AML) is characterized by the accumulation of 
      undifferentiated blast cells in the bone marrow and blood. In most cases of AML, 
      relapse frequently occurs due to resistance to chemotherapy. Compelling research 
      results indicate that drug resistance in cancer cells is highly dependent on the 
      intracellular levels of reactive oxygen species (ROS). Modulating ROS levels is 
      therefore a valuable strategy to overcome the chemotherapy resistance of leukemic 
      cells. In this study, we evaluated the efficiency of diphenyleneiodonium (DPI)-a 
      well-known inhibitor of ROS production-in targeting AML cells. Results showed 
      that although inhibiting cytoplasmic ROS production, DPI also triggered an 
      increase in the mitochondrial ROS levels, caused by the disruption of the 
      mitochondrial respiratory chain. We also demonstrated that DPI blocks 
      mitochondrial oxidative phosphorylation (OxPhos) in a dose-dependent manner, and 
      that AML cells with high OxPhos status are highly sensitive to treatment with 
      DPI, which synergizes with the chemotherapeutic agent cytarabine (Ara-C). Thus, 
      our results suggest that targeting mitochondrial function with DPI might be 
      exploited to target AML cells with high OxPhos status.
FAU - Dakik, Hassan
AU  - Dakik H
AUID- ORCID: 0000-0003-0270-8195
AD  - EA7501 GICC/CNRS ERL7001 LNOx, University of Tours, F-37032 Tours, France.
FAU - El Dor, Maya
AU  - El Dor M
AD  - EA7501 GICC/CNRS ERL7001 LNOx, University of Tours, F-37032 Tours, France.
FAU - Bourgeais, Jerome
AU  - Bourgeais J
AD  - EA7501 GICC/CNRS ERL7001 LNOx, University of Tours, F-37032 Tours, France.
AD  - Department of Biological Hematology, Tours University Hospital, F-37000 Tours, 
      France.
FAU - Kouzi, Farah
AU  - Kouzi F
AD  - EA7501 GICC/CNRS ERL7001 LNOx, University of Tours, F-37032 Tours, France.
AD  - Biology Department, Faculty of Sciences, Lebanese University, Beirut 90656, 
      Lebanon.
FAU - Herault, Olivier
AU  - Herault O
AUID- ORCID: 0000-0002-7419-1124
AD  - EA7501 GICC/CNRS ERL7001 LNOx, University of Tours, F-37032 Tours, France.
AD  - Department of Biological Hematology, Tours University Hospital, F-37000 Tours, 
      France.
FAU - Gouilleux, Fabrice
AU  - Gouilleux F
AUID- ORCID: 0000-0001-6047-1718
AD  - EA7501 GICC/CNRS ERL7001 LNOx, University of Tours, F-37032 Tours, France.
FAU - Zibara, Kazem
AU  - Zibara K
AUID- ORCID: 0000-0002-9887-072X
AD  - Biology Department, Faculty of Sciences, Lebanese University, Beirut 90656, 
      Lebanon.
AD  - ER045, PRASE, Beirut 6573/14, Lebanon.
FAU - Mazurier, Frederic
AU  - Mazurier F
AUID- ORCID: 0000-0002-6984-7096
AD  - EA7501 GICC/CNRS ERL7001 LNOx, University of Tours, F-37032 Tours, France.
LA  - eng
GR  - N/A/Hubert Curien Program/
GR  - N/A/Ligue Contre le Cancer Grand-Ouest/
GR  - N/A/Lebanese University/
GR  - N/A/Lebanese National Council for Scientific Research/
GR  - N/A/Fondation ARC pour la Recherche sur le Cancer/
GR  - N/A/Lebanese south governate/
PT  - Journal Article
DEP - 20220518
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9140039
OTO - NOTNLM
OT  - Ara-C
OT  - DPI
OT  - OxPhos
OT  - leukemia
OT  - mitochondria
OT  - oxidative stress
COIS- The authors declare no conflict of interest.
EDAT- 2022/05/29 06:00
MHDA- 2022/05/29 06:01
PMCR- 2022/05/18
CRDT- 2022/05/28 01:09
PHST- 2021/12/07 00:00 [received]
PHST- 2022/05/09 00:00 [revised]
PHST- 2022/05/11 00:00 [accepted]
PHST- 2022/05/28 01:09 [entrez]
PHST- 2022/05/29 06:00 [pubmed]
PHST- 2022/05/29 06:01 [medline]
PHST- 2022/05/18 00:00 [pmc-release]
AID - cancers14102485 [pii]
AID - cancers-14-02485 [pii]
AID - 10.3390/cancers14102485 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 May 18;14(10):2485. doi: 10.3390/cancers14102485.