New findings on the action of hypericin in hypoxic cancer cells with a focus on the modulation of side population cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F23%3A00131566" target="_blank" >RIV/00216224:14740/23:00131566 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0753332223006194?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0753332223006194?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.biopha.2023.114829" target="_blank" >10.1016/j.biopha.2023.114829</a>

Result language

angličtina

Original language name

New findings on the action of hypericin in hypoxic cancer cells with a focus on the modulation of side population cells

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/LM2023042" target="_blank" >LM2023042: Czech Infrastructure for Integrative Structural Biology</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biomedicine and Pharmacotherapy

ISSN

0753-3322

e-ISSN

1950-6007

Volume of the periodical

163

Issue of the periodical within the volume

July

Country of publishing house

FR - FRANCE

Number of pages

15

Pages from-to

1-15

UT code for WoS article

000998460000001

EID of the result in the Scopus database

2-s2.0-85154071734