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...
Main Authors: | , , , , , , |
---|---|
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 |