PMID- 33916015
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231111
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 7
DP  - 2021 Apr 1
TI  - Death Receptor 5 (TNFRSF10B) Is Upregulated and TRAIL Resistance Is Reversed in 
      Hypoxia and Normoxia in Colorectal Cancer Cell Lines after Treatment with Skyrin, 
      the Active Metabolite of Hypericum spp.
LID - 10.3390/cancers13071646 [doi]
LID - 1646
AB  - Skyrin (SKR) is a plant bisanthraquinone secondary metabolite from the Hypericum 
      genus with potential use in anticancer therapy. However, its effect and mechanism 
      of action are still unknown. The negative effect of SKR on HCT 116 and HT-29 
      cancer cell lines in hypoxic and normoxic conditions was observed. HCT 116 cells 
      were more responsive to SKR treatment as demonstrated by decreased metabolic 
      activity, cellularity and accumulation of cells in the G1 phase. Moreover, an 
      increasing number of apoptotic cells was observed after treatment with SKR. Based 
      on the LC-MS comparative proteomic data from hypoxia and normoxia (data are 
      available via ProteomeXchange with the identifier PXD019995), SKR significantly 
      upregulated Death receptor 5 (DR5), which was confirmed by real-time qualitative 
      PCR (RT-qPCR). Furthermore, multiple changes in the Tumor necrosis factor-related 
      apoptosis-inducing ligand (TRAIL)-activated cascade were observed. Moreover, the 
      reversion of TRAIL resistance was observed in HCT 116, HT-29 and SW620 cell 
      lines, even in hypoxia, which was linked to the upregulation of DR5. In 
      conclusion, our results propose the use of SKR as a prospective anticancer drug, 
      particularly as an adjuvant to TRAIL-targeting treatment to reverse TRAIL 
      resistance in hypoxia.
FAU - Babincak, Marian
AU  - Babincak M
AUID- ORCID: 0000-0002-2540-5608
AD  - Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Safarik 
      University in Kosice, Srobarova 2, 041 54 Kosice, Slovakia.
FAU - Jendzelovsky, Rastislav
AU  - Jendzelovsky R
AUID- ORCID: 0000-0001-6338-0723
AD  - Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Safarik 
      University in Kosice, Srobarova 2, 041 54 Kosice, Slovakia.
FAU - Kosuth, Jan
AU  - Kosuth J
AUID- ORCID: 0000-0001-5584-8728
AD  - Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Safarik 
      University in Kosice, Srobarova 2, 041 54 Kosice, Slovakia.
FAU - Majernik, Martin
AU  - Majernik M
AUID- ORCID: 0000-0002-0479-7059
AD  - Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Safarik 
      University in Kosice, Srobarova 2, 041 54 Kosice, Slovakia.
FAU - Vargova, Jana
AU  - Vargova J
AUID- ORCID: 0000-0002-4066-3453
AD  - Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Safarik 
      University in Kosice, Srobarova 2, 041 54 Kosice, Slovakia.
FAU - Mikulasek, Kamil
AU  - Mikulasek K
AD  - Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 
      Brno, Czech Republic.
AD  - National Centre for Biomolecular Research, Faculty of Science, Masaryk 
      University, Kamenice 5, 625 00 Brno, Czech Republic.
FAU - Zdrahal, Zbynek
AU  - Zdrahal Z
AUID- ORCID: 0000-0003-3044-5548
AD  - Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 
      Brno, Czech Republic.
AD  - National Centre for Biomolecular Research, Faculty of Science, Masaryk 
      University, Kamenice 5, 625 00 Brno, Czech Republic.
FAU - Fedorocko, Peter
AU  - Fedorocko P
AUID- ORCID: 0000-0002-1138-6282
AD  - Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Safarik 
      University in Kosice, Srobarova 2, 041 54 Kosice, Slovakia.
LA  - eng
GR  - APVV-18-0125/Agentura na Podporu Vyskumu a Vyvoja/
GR  - VEGA 1/0022/19/Ministerstvo skolstva, vedy, vyskumu a sportu Slovenskej 
      republiky/
GR  - ITMS 26220220185/Operational Programme Research and Development Programme, funded 
      by the ERDF/
GR  - ITMS2014+: 313011D103/Operational Programme Research and Development Programme, 
      funded by the ERDF/
GR  - LQ1601/MEYS CR/
GR  - LM2018127/MEYS CR/
GR  - LM2015043/MEYS CR/
GR  - LM2018140/MEYS CR/
PT  - Journal Article
DEP - 20210401
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8036732
OTO - NOTNLM
OT  - Death receptor 5
OT  - Hypericum
OT  - TRAIL
OT  - TRAIL resistance
OT  - colorectal cancer
OT  - hypoxia
OT  - proteomics
OT  - skyrin
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2021/05/01 06:00
MHDA- 2021/05/01 06:01
PMCR- 2021/04/01
CRDT- 2021/04/30 01:01
PHST- 2020/12/17 00:00 [received]
PHST- 2021/03/26 00:00 [revised]
PHST- 2021/03/29 00:00 [accepted]
PHST- 2021/04/30 01:01 [entrez]
PHST- 2021/05/01 06:00 [pubmed]
PHST- 2021/05/01 06:01 [medline]
PHST- 2021/04/01 00:00 [pmc-release]
AID - cancers13071646 [pii]
AID - cancers-13-01646 [pii]
AID - 10.3390/cancers13071646 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Apr 1;13(7):1646. doi: 10.3390/cancers13071646.