PMID- 32205093
OWN - NLM
STAT- MEDLINE
DCOM- 20201022
LR  - 20201022
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 175
DP  - 2020 May
TI  - HIF-1 stabilization exerts anticancer effects in breast cancer cells in vitro and 
      in vivo.
PG  - 113922
LID - S0006-2952(20)30150-7 [pii]
LID - 10.1016/j.bcp.2020.113922 [doi]
AB  - Tumor hypoxia and high activity of hypoxia-inducible factor-1 (HIF-1) correlate 
      with adverse disease outcomes, malignancy, resistance to therapy and metastasis. 
      Nonetheless, recent studies indicate that under certain circumstances, HIF-1 
      stabilization may exert protective effects and even decrease tumor cell 
      aggressiveness. This study aimed to characterize the potential anticancer effect 
      of molidustat (BAY 85-3934), the prolyl hydroxylase (PHD) inhibitor and HIF-1 
      stabilizator. We confirmed that molidustat stabilizes HIF-1alpha and induces the 
      expression of vascular endothelial growth factor (VEGF) in MDA-MB-231 breast 
      cancer cells, to a similar or even greater extent than hypoxia. Interestingly, 
      decreased cell survival and colony formation capabilities, together with S/G2 
      cell cycle arrest, were observed after treatment with PHD inhibitor. Importantly, 
      molidustat enhanced the effectiveness of the chemotherapeutic drug, gemcitabine, 
      on cancer cells. Finally, the xenograft model revealed decreased tumor growth in 
      vivo after molidustat treatment. Both in vitro and in vivo analysis showed no 
      differences in the angiogenic potential of endothelial cells treated with 
      tumor-conditioned media or vascularization of the MDA-MB-231 xenografts, 
      respectively. In summary, molidustat treatment exhibits an inhibitory effect on 
      breast cancer cell survival, self-renewal capacity and potentiates the efficacy 
      of chemotherapeutic gemcitabine.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Kachamakova-Trojanowska, Neli
AU  - Kachamakova-Trojanowska N
AD  - Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland; 
      Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 
      30-387 Krakow, Poland.
FAU - Podkalicka, Paulina
AU  - Podkalicka P
AD  - Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
FAU - Bogacz, Tomasz
AU  - Bogacz T
AD  - Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
FAU - Barwacz, Szymon
AU  - Barwacz S
AD  - Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
FAU - Jozkowicz, Alicja
AU  - Jozkowicz A
AD  - Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
FAU - Dulak, Jozef
AU  - Dulak J
AD  - Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
FAU - Loboda, Agnieszka
AU  - Loboda A
AD  - Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland. 
      Electronic address: agnieszka.loboda@uj.edu.pl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200320
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Antineoplastic Agents)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Pyrazoles)
RN  - 0 (Triazoles)
RN  - 9JH486CZ13 (molidustat)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Breast Neoplasms/drug therapy/*metabolism
MH  - Cell Line, Tumor
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Protein Stability/drug effects
MH  - Pyrazoles/*pharmacology/therapeutic use
MH  - Random Allocation
MH  - Triazoles/*pharmacology/therapeutic use
MH  - Xenograft Model Antitumor Assays/methods
OTO - NOTNLM
OT  - Angiogenesis
OT  - Breast cancer
OT  - HIF-1
OT  - Prolyl hydroxylase inhibitor
OT  - Tumorigenesis
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/03/25 06:00
MHDA- 2020/10/23 06:00
CRDT- 2020/03/25 06:00
PHST- 2019/12/22 00:00 [received]
PHST- 2020/03/19 00:00 [accepted]
PHST- 2020/03/25 06:00 [pubmed]
PHST- 2020/10/23 06:00 [medline]
PHST- 2020/03/25 06:00 [entrez]
AID - S0006-2952(20)30150-7 [pii]
AID - 10.1016/j.bcp.2020.113922 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2020 May;175:113922. doi: 10.1016/j.bcp.2020.113922. Epub 2020 
      Mar 20.