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@article{2305498,
author = {Buľková, Viktória and Vargová, Jana and Babinčák, Marián and Jendželovský, Rastislav and Zdráhal, Zbyněk and Roudnický, Pavel and Košuth, Ján and Fedoročko, Peter},
article_number = {July},
doi = {http://dx.doi.org/10.1016/j.biopha.2023.114829},
keywords = {Hypericin; Hypoxia; Breast cancer resistance protein; Side population; ECM reorganization; Proteomics},
language = {eng},
issn = {0753-3322},
journal = {Biomedicine and Pharmacotherapy},
title = {New findings on the action of hypericin in hypoxic cancer cells with a focus on the modulation of side population cells},
url = {https://www.sciencedirect.com/science/article/pii/S0753332223006194?via%3Dihub},
volume = {163},
year = {2023}
}
TY - JOUR
ID - 2305498
AU - Buľková, Viktória - Vargová, Jana - Babinčák, Marián - Jendželovský, Rastislav - Zdráhal, Zbyněk - Roudnický, Pavel - Košuth, Ján - Fedoročko, Peter
PY - 2023
TI - New findings on the action of hypericin in hypoxic cancer cells with a focus on the modulation of side population cells
JF - Biomedicine and Pharmacotherapy
VL - 163
IS - July
SP - 1-15
EP - 1-15
PB - Elsevier
SN - 07533322
KW - Hypericin
KW - Hypoxia
KW - Breast cancer resistance protein
KW - Side population
KW - ECM reorganization
KW - Proteomics
UR - https://www.sciencedirect.com/science/article/pii/S0753332223006194?via%3Dihub
N2 - The presence of key hypoxia regulators, namely, hypoxia-inducible factor (HIF)-1 alpha or HIF-2 alpha, in tumors is associated with poor patient prognosis. Hypoxia massively activates several genes, including the one encoding the BCRP transporter that proffers multidrug resistance to cancer cells through the xenobiotic efflux and is a determinant of the side population (SP) associated with cancer stem-like phenotypes. As natural medicine comes to the fore, it is instinctive to look for natural agents possessing powerful features against cancer resistance. Hypericin, a pleiotropic agent found in Hypericum plants, is a good example as it is a BCRP substrate and po-tential inhibitor, and an SP and HIF modulator. Here, we showed that hypericin efficiently accumulated in hypoxic cancer cells, degraded HIF-1/2 alpha, and decreased BCRP efflux together with hypoxia, thus diminishing the SP population. On the contrary, this seemingly favorable result was accompanied by the stimulated migration of this minor population that preserved the SP phenotype. Because hypoxia unexpectedly decreased the BCRP level and SP fraction, we compared the SP and non-SP proteomes and their changes under hypoxia in the A549 cell line. We identified differences among protein groups connected to the epithelial-mesenchymal transition, although major changes were related to hypoxia, as the upregulation of many proteins, including serpin E1, PLOD2 and LOXL2, that ultimately contribute to the initiation of the metastatic cascade was detected. Alto-gether, this study helps in clarifying the innate and hypoxia-triggered resistance of cancer cells and highlights the ambivalent role of natural agents in the biology of these cells.
ER -
BUĽKOVÁ, Viktória, Jana VARGOVÁ, Marián BABINČÁK, Rastislav JENDŽELOVSKÝ, Zbyněk ZDRÁHAL, Pavel ROUDNICKÝ, Ján KOŠUTH and Peter FEDOROČKO. New findings on the action of hypericin in hypoxic cancer cells with a focus on the modulation of side population cells. \textit{Biomedicine and Pharmacotherapy}. Elsevier, 2023, vol.~163, July, p.~1-15. ISSN~0753-3322. Available from: https://dx.doi.org/10.1016/j.biopha.2023.114829.
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