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.

J 2021

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.

BABINČÁK, Marián, Rastislav JENŽELOVSKÝ, Ján KOŠUTH, Martin MAJERNÍK, Jana VARGOVÁ et. al.

Základní údaje

Originální název

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.

Autoři

BABINČÁK, Marián (703 Slovensko), Rastislav JENŽELOVSKÝ (703 Slovensko), Ján KOŠUTH, Martin MAJERNÍK, Jana VARGOVÁ, Kamil MIKULÁŠEK (203 Česká republika, domácí), Zbyněk ZDRÁHAL (203 Česká republika, garant, domácí) a Peter FEDOROČKO (703 Slovensko)

Vydání

Cancers, 2021, 2072-6694

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

fulltext

Impakt faktor

Impact factor: 6.575

Kód RIV

RIV/00216224:14740/21:00123880

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.3390/cancers13071646

UT WoS

000638320900001

Klíčová slova anglicky

skyrin; hypoxia; colorectal cancer; proteomics; Death receptor 5; TRAIL; TRAIL resistance; Hypericum

Štítky

CF PROT, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 10. 10. 2024 14:40, Ing. Martina Blahová

Anotace

V originále

Hypoxic conditions are common in solid tumors and are very often connected with the poor prognosis of cancer patients. The lack of oxygen often causes the failure of therapy due to multiple mechanisms increasing cancer survival. Skyrin (SKR) is a secondary plant metabolite from the genus Hypericum spp., with a potential anticancer effects but still unknown mechanism of action. Based on our comprehensive analysis of SKR action, SKR shows significant efficiency against cancer, but not healthy cells, induces apoptosis, and upregulates Death receptor 5 in cancer cells in normoxic, as well as hypoxic conditions. SKR reverses TRAIL resistance even in TRAIL-resistant cancer cell lines in hypoxia. To sum up, SKR can be possibly used as a natural antitumor drug per se or as an adjuvant to TRAIL treatment in hypoxic and therapy-resistant tumors. 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.

Návaznosti

LM2015043, projekt VaV

Název: Česká infrastruktura pro integrativní strukturní biologii (Akronym: CIISB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Czech Infrastructure for Integrative Structural Biology

LM2018127, projekt VaV

Název: Česká infrastruktura pro integrativní strukturní biologii (Akronym: CIISB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Czech Infrastructure for Integrative Structural Biology

LM2018140, projekt VaV

Název: e-Infrastruktura CZ (Akronym: e-INFRA CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, e-Infrastruktura CZ

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

90043, velká výzkumná infrastruktura

Název: CIISB

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

BABINČÁK, Marián, Rastislav JENŽELOVSKÝ, Ján KOŠUTH, Martin MAJERNÍK, Jana VARGOVÁ, Kamil MIKULÁŠEK, Zbyněk ZDRÁHAL a Peter FEDOROČKO. 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. Cancers. 2021, roč. 13, č. 7, s. "1646", 30 s. ISSN 2072-6694. Dostupné z: https://dx.doi.org/10.3390/cancers13071646.

@article{1824739,
   author = {Babinčák, Marián and Jenželovský, Rastislav and Košuth, Ján and Majerník, Martin and Vargová, Jana and Mikulášek, Kamil and Zdráhal, Zbyněk and Fedoročko, Peter},
   article_number = {7},
   doi = {http://dx.doi.org/10.3390/cancers13071646},
   keywords = {skyrin; hypoxia; colorectal cancer; proteomics; Death receptor 5; TRAIL; TRAIL resistance; Hypericum},
   language = {eng},
   issn = {2072-6694},
   journal = {Cancers},
   title = {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.},
   url = {https://www.mdpi.com/2072-6694/13/7/1646},
   volume = {13},
   year = {2021}
}

TY  - JOUR
ID  - 1824739
AU  - Babinčák, Marián - Jenželovský, Rastislav - Košuth, Ján - Majerník, Martin - Vargová, Jana - Mikulášek, Kamil - Zdráhal, Zbyněk - Fedoročko, Peter
PY  - 2021
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.
JF  - Cancers
VL  - 13
IS  - 7
SP  - "1646"
EP  - "1646"
SN  - 20726694
KW  - skyrin
KW  - hypoxia
KW  - colorectal cancer
KW  - proteomics
KW  - Death receptor 5
KW  - TRAIL
KW  - TRAIL resistance
KW  - Hypericum
UR  - https://www.mdpi.com/2072-6694/13/7/1646
N2  - Hypoxic conditions are common in solid tumors and are very often connected with the poor prognosis of cancer patients. The lack of oxygen often causes the failure of therapy due to multiple mechanisms increasing cancer survival. Skyrin (SKR) is a secondary plant metabolite from the genus Hypericum spp., with a potential anticancer effects but still unknown mechanism of action. Based on our comprehensive analysis of SKR action, SKR shows significant efficiency against cancer, but not healthy cells, induces apoptosis, and upregulates Death receptor 5 in cancer cells in normoxic, as well as hypoxic conditions. SKR reverses TRAIL resistance even in TRAIL-resistant cancer cell lines in hypoxia. To sum up, SKR can be possibly used as a natural antitumor drug per se or as an adjuvant to TRAIL treatment in hypoxic and therapy-resistant tumors. 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.
ER  -

BABINČÁK, Marián, Rastislav JENŽELOVSKÝ, Ján KOŠUTH, Martin MAJERNÍK, Jana VARGOVÁ, Kamil MIKULÁŠEK, Zbyněk ZDRÁHAL a Peter FEDOROČKO. 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. \textit{Cancers}. 2021, roč.~13, č.~7, s.~''1646'', 30 s. ISSN~2072-6694. Dostupné z: https://dx.doi.org/10.3390/cancers13071646.

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