Differential Response of Lung Cancer Cells, with Various Driver Mutations, to Plant Polyphenol Resveratrol and Vitamin D Active Metabolite PRI-2191

Plant polyphenols and vitamins D exhibit chemopreventive and therapeutic anticancer effects. We first evaluated the biological effects of the plant polyphenol resveratrol (RESV) and vitamin D active metabolite PRI-2191 on lung cancer cells having different genetic backgrounds. RESV and PRI-2191 show...

Full description

Bibliographic Details
Main Authors: Ewa Maj, Beata Maj, Klaudia Bobak, Michalina Gos, Michał Chodyński, Andrzej Kutner, Joanna Wietrzyk
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/5/2354
_version_ 1797395079527137280
author Ewa Maj
Beata Maj
Klaudia Bobak
Michalina Gos
Michał Chodyński
Andrzej Kutner
Joanna Wietrzyk
author_facet Ewa Maj
Beata Maj
Klaudia Bobak
Michalina Gos
Michał Chodyński
Andrzej Kutner
Joanna Wietrzyk
author_sort Ewa Maj
collection DOAJ
description Plant polyphenols and vitamins D exhibit chemopreventive and therapeutic anticancer effects. We first evaluated the biological effects of the plant polyphenol resveratrol (RESV) and vitamin D active metabolite PRI-2191 on lung cancer cells having different genetic backgrounds. RESV and PRI-2191 showed divergent responses depending on the genetic profile of cells. Antiproliferative activity of PRI-2191 was noticeable in EGFRmut cells, while RESV showed the highest antiproliferative and caspase-3-inducing activity in KRASmut cells. RESV upregulated p53 expression in wtp53 cells, while downregulated it in mutp53 cells with simultaneous upregulation of p21 expression in both cases. The effect of PRI-2191 on the induction of CYP24A1 expression was enhanced by RESV in two KRASmut cell lines. The effect of RESV combined with PRI-2191 on cytokine production was pronounced and modulated. RESV cooperated with PRI-2191 in regulating the expression of IL-8 in EGFRmut cells, while OPN in KRASmut cells and PD-L1 in both cell subtypes. We hypothesize that the differences in response to RESV and PRI-2191 between EGFRmut and KRASmut cell lines result from the differences in epigenetic modifications since both cell subtypes are associated with the divergent smoking history that can induce epigenetic alterations.
first_indexed 2024-03-09T00:29:12Z
format Article
id doaj.art-359c170851944901ae18ff64489fe4bd
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-09T00:29:12Z
publishDate 2021-02-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-359c170851944901ae18ff64489fe4bd2023-12-11T18:39:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01225235410.3390/ijms22052354Differential Response of Lung Cancer Cells, with Various Driver Mutations, to Plant Polyphenol Resveratrol and Vitamin D Active Metabolite PRI-2191Ewa Maj0Beata Maj1Klaudia Bobak2Michalina Gos3Michał Chodyński4Andrzej Kutner5Joanna Wietrzyk6Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla, 53-114 Wrocław, PolandHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla, 53-114 Wrocław, PolandHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla, 53-114 Wrocław, PolandHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla, 53-114 Wrocław, PolandŁukasiewicz Research Network—Industrial Chemistry Institute, 8 Rydygiera, 01-793 Warsaw, PolandFaculty of Mathematics and Natural Sciences, School of Sciences, Institute of Chemical Sciences, Cardinal Stefan Wyszyński University in Warsaw, 1/3 Wóycickiego, 01-938 Warsaw, PolandHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla, 53-114 Wrocław, PolandPlant polyphenols and vitamins D exhibit chemopreventive and therapeutic anticancer effects. We first evaluated the biological effects of the plant polyphenol resveratrol (RESV) and vitamin D active metabolite PRI-2191 on lung cancer cells having different genetic backgrounds. RESV and PRI-2191 showed divergent responses depending on the genetic profile of cells. Antiproliferative activity of PRI-2191 was noticeable in EGFRmut cells, while RESV showed the highest antiproliferative and caspase-3-inducing activity in KRASmut cells. RESV upregulated p53 expression in wtp53 cells, while downregulated it in mutp53 cells with simultaneous upregulation of p21 expression in both cases. The effect of PRI-2191 on the induction of CYP24A1 expression was enhanced by RESV in two KRASmut cell lines. The effect of RESV combined with PRI-2191 on cytokine production was pronounced and modulated. RESV cooperated with PRI-2191 in regulating the expression of IL-8 in EGFRmut cells, while OPN in KRASmut cells and PD-L1 in both cell subtypes. We hypothesize that the differences in response to RESV and PRI-2191 between EGFRmut and KRASmut cell lines result from the differences in epigenetic modifications since both cell subtypes are associated with the divergent smoking history that can induce epigenetic alterations.https://www.mdpi.com/1422-0067/22/5/2354anticancer activitylung cancerresveratrolPRI-2191vitamin D
spellingShingle Ewa Maj
Beata Maj
Klaudia Bobak
Michalina Gos
Michał Chodyński
Andrzej Kutner
Joanna Wietrzyk
Differential Response of Lung Cancer Cells, with Various Driver Mutations, to Plant Polyphenol Resveratrol and Vitamin D Active Metabolite PRI-2191
International Journal of Molecular Sciences
anticancer activity
lung cancer
resveratrol
PRI-2191
vitamin D
title Differential Response of Lung Cancer Cells, with Various Driver Mutations, to Plant Polyphenol Resveratrol and Vitamin D Active Metabolite PRI-2191
title_full Differential Response of Lung Cancer Cells, with Various Driver Mutations, to Plant Polyphenol Resveratrol and Vitamin D Active Metabolite PRI-2191
title_fullStr Differential Response of Lung Cancer Cells, with Various Driver Mutations, to Plant Polyphenol Resveratrol and Vitamin D Active Metabolite PRI-2191
title_full_unstemmed Differential Response of Lung Cancer Cells, with Various Driver Mutations, to Plant Polyphenol Resveratrol and Vitamin D Active Metabolite PRI-2191
title_short Differential Response of Lung Cancer Cells, with Various Driver Mutations, to Plant Polyphenol Resveratrol and Vitamin D Active Metabolite PRI-2191
title_sort differential response of lung cancer cells with various driver mutations to plant polyphenol resveratrol and vitamin d active metabolite pri 2191
topic anticancer activity
lung cancer
resveratrol
PRI-2191
vitamin D
url https://www.mdpi.com/1422-0067/22/5/2354
work_keys_str_mv AT ewamaj differentialresponseoflungcancercellswithvariousdrivermutationstoplantpolyphenolresveratrolandvitamindactivemetabolitepri2191
AT beatamaj differentialresponseoflungcancercellswithvariousdrivermutationstoplantpolyphenolresveratrolandvitamindactivemetabolitepri2191
AT klaudiabobak differentialresponseoflungcancercellswithvariousdrivermutationstoplantpolyphenolresveratrolandvitamindactivemetabolitepri2191
AT michalinagos differentialresponseoflungcancercellswithvariousdrivermutationstoplantpolyphenolresveratrolandvitamindactivemetabolitepri2191
AT michałchodynski differentialresponseoflungcancercellswithvariousdrivermutationstoplantpolyphenolresveratrolandvitamindactivemetabolitepri2191
AT andrzejkutner differentialresponseoflungcancercellswithvariousdrivermutationstoplantpolyphenolresveratrolandvitamindactivemetabolitepri2191
AT joannawietrzyk differentialresponseoflungcancercellswithvariousdrivermutationstoplantpolyphenolresveratrolandvitamindactivemetabolitepri2191