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@article{1600956,
author = {Vargova, Jana and Mikes, Jaromir and Jendzelovsky, Rastislav and Mikesova, Lucia and Kucharova, Barbora and Culka, Lubomir and Fedr, Radek and Remsik, Jan and Soucek, Karel and Kozubík, Alois and Fedorocko, Peter},
article_location = {Issy-les-Moulineaux},
article_number = {MAR},
doi = {http://dx.doi.org/10.1016/j.biopha.2018.01.074},
keywords = {Side population; Hypericin; St. John's wort; ABC transporters; Cancer stem-like cells; Drug resistance},
language = {eng},
issn = {0753-3322},
journal = {BIOMEDICINE & PHARMACOTHERAPY},
title = {Hypericin affects cancer side populations via competitive inhibition of BCRP},
url = {https://www.sciencedirect.com/science/article/pii/S0753332217361012},
volume = {99},
year = {2018}
}
TY - JOUR
ID - 1600956
AU - Vargova, Jana - Mikes, Jaromir - Jendzelovsky, Rastislav - Mikesova, Lucia - Kucharova, Barbora - Culka, Lubomir - Fedr, Radek - Remsik, Jan - Soucek, Karel - Kozubík, Alois - Fedorocko, Peter
PY - 2018
TI - Hypericin affects cancer side populations via competitive inhibition of BCRP
JF - BIOMEDICINE & PHARMACOTHERAPY
VL - 99
IS - MAR
SP - 511-522
EP - 511-522
PB - ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
SN - 07533322
KW - Side population
KW - Hypericin
KW - St. John's wort
KW - ABC transporters
KW - Cancer stem-like cells
KW - Drug resistance
UR - https://www.sciencedirect.com/science/article/pii/S0753332217361012
L2 - https://www.sciencedirect.com/science/article/pii/S0753332217361012
N2 - Objective: Cancer stem-like cells (CSLCs) are considered a root of tumorigenicity and resistance. However, their identification remains challenging. The use of the side population (SP) assay as a credible marker of CSLCs remains controversial. The SP assay relies on the elevated activity of ABC transporters that, in turn, can be modulated by hypericin (HYP), a photosensitizer and bioactive compound of St. John's Wort (Hypericum perforatum), a popular over-the-counter antidepressant. Here we aimed to comprehensively characterize the SP phenotype of cancer cells and to determine the impact of HYP on these cells. Methods: Flow cytometry and sorting-based assays were employed, including CD24-, CD44-, CD133-, and ALDH-positivity, clonogenicity, 3D-forming ability, ABC transporter expression and activity, and intracellular accumulation of HYP/Hoechst 33342. The tumorigenic ability of SP, nonSP, and HYP-treated cells was verified by xenotransplantation into immunodeficient mice. Results: The SP phenotype was associated with elevated expression of several investigated transporters and more intensive growth in non-adherent conditions but not with higher clonogenicity, tumorigenicity or ALDH-positivity. Despite stimulated BCRP level and MRP1 activity, HYP reversibly decreased the SP proportion, presumably via competitive inhibition of BCRP. HYP-selected SP cells acquired additional traits of resistance and extensively eliminated HYP. Conclusions: Our results suggest that SP is not an unequivocal CSLC-marker. However, SP could play an important role in modulating HYP-treatment and serve as a negative predictive tool for HYP-based therapies. Moreover, the use of supplements containing HYP by cancer patients should be carefully considered, due to its proposed effect on drug efflux and complex impact on tumor cells, which have not yet been sufficiently characterized.
ER -
VARGOVA, Jana, Jaromir MIKES, Rastislav JENDZELOVSKY, Lucia MIKESOVA, Barbora KUCHAROVA, Lubomir CULKA, Radek FEDR, Jan REMSIK, Karel SOUCEK, Alois KOZUBÍK a Peter FEDOROCKO. Hypericin affects cancer side populations via competitive inhibition of BCRP. \textit{BIOMEDICINE \&{} PHARMACOTHERAPY}. Issy-les-Moulineaux: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2018, roč.~99, MAR, s.~511-522. ISSN~0753-3322. Dostupné z: https://dx.doi.org/10.1016/j.biopha.2018.01.074.
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