Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F17%3A00473195" target="_blank" >RIV/86652036:_____/17:00473195 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/17:00473195 RIV/00216208:11120/17:43913165

Result on the web

<a href="http://dx.doi.org/10.1038/srep44497" target="_blank" >http://dx.doi.org/10.1038/srep44497</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/srep44497" target="_blank" >10.1038/srep44497</a>

Result language

angličtina

Original language name

Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

Original language description

The development of drug resistance is a major problem which often occurs during anticancer chemotherapies. Photodynamic therapy (PDT) has been studied as an alternative treatment modality for drug-resistant tumors, however the question of resistance to PDT and potential cross-resistance with chemotherapy has yet to be fully answered. To investigate the mechanism of resistance to PDT, we developed an in vitro experimental model system in a mouse mammary carcinoma cell line 4T1. We used two ethylene glycol derivatives of tetraphenylporphyrin, and tetraphenylchlorin derivative, temoporfin, as photosensitizers (PS). PDT-resistant clones were obtained by exposure to a set concentration of PS followed by irradiation with increasing light doses. PDT resistance to soluble glycol porphyrins was mediated mainly by increased drug efflux through ABCB1 (P-glycoprotein) as we demonstrated by specific ABCB1 knockdown experiments, which in turn rescued the sensitivity of resistant cells to PDT. In contrast, resistance raised to temoporfin, which is generally more lipophilic than glycol porphyrins, elicited mechanism based on sequestration of the drug to lysosomes. The resistance that is acquired from a particular PS could be overcome by using a different PS, which is not susceptible to the same mechanism(s) of resistance. Elucidation of the underlying mechanisms in various types of resistance might facilitate improvements in PDT treatment design.

Czech name

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Czech description

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Type

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

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/LO1220" target="_blank" >LO1220: CZ-OPENSCREEN: National infrastructure for chemical biology</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

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

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

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Volume of the periodical

7

Issue of the periodical within the volume

Mar 15

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

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UT code for WoS article

000396339500001

EID of the result in the Scopus database

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