Cargando…

Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT

In the current study, we identified a mechanism of resveratrol (RES) underlying its anti-cancer properties against human ovarian adenocarcinoma SKOV-3 cells. We investigated its anti-proliferative and apoptosis-inducing effects in combination with cisplatin, using cell viability assay, flow cytometr...

Descripción completa

Detalles Bibliográficos
Autores principales: Hankittichai, Phateep, Thaklaewphan, Phatarawat, Wikan, Nitwara, Ruttanapattanakul, Jirapak, Potikanond, Saranyapin, Smith, Duncan R., Nimlamool, Wutigri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10220637/
https://www.ncbi.nlm.nih.gov/pubmed/37242538
http://dx.doi.org/10.3390/ph16050755
_version_ 1785049265361387520
author Hankittichai, Phateep
Thaklaewphan, Phatarawat
Wikan, Nitwara
Ruttanapattanakul, Jirapak
Potikanond, Saranyapin
Smith, Duncan R.
Nimlamool, Wutigri
author_facet Hankittichai, Phateep
Thaklaewphan, Phatarawat
Wikan, Nitwara
Ruttanapattanakul, Jirapak
Potikanond, Saranyapin
Smith, Duncan R.
Nimlamool, Wutigri
author_sort Hankittichai, Phateep
collection PubMed
description In the current study, we identified a mechanism of resveratrol (RES) underlying its anti-cancer properties against human ovarian adenocarcinoma SKOV-3 cells. We investigated its anti-proliferative and apoptosis-inducing effects in combination with cisplatin, using cell viability assay, flow cytometry, immunofluorescence study and Western blot analysis. We discovered that RES suppressed cancer cell proliferation and stimulated apoptosis, especially when combined with cisplatin. This compound also inhibited SKOV-3 cell survival, which may partly be due to its potential to inhibit protein kinase B (AKT) phosphorylation and induce the S-phase cell cycle arrest. RES in combination with cisplatin strongly induced cancer cell apoptosis through activating the caspase-dependent cascade, which was associated with its ability to stimulate nuclear phosphorylation of p38 mitogen-activated protein kinase (MAPK), well recognized to be involved in transducing environmental stress signals. RES-induced p38 phosphorylation was very specific, and the activation status of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) was not mainly affected. Taken together, our study provides accumulated evidence that RES represses proliferation and promotes apoptosis in SKOV-3 ovarian cancer cells through activating the p38 MAPK pathway. It is interesting that this active compound may be used as an effective agent to sensitize ovarian cancer to apoptosis induced by standard chemotherapies.
format Online
Article
Text
id pubmed-10220637
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-102206372023-05-28 Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT Hankittichai, Phateep Thaklaewphan, Phatarawat Wikan, Nitwara Ruttanapattanakul, Jirapak Potikanond, Saranyapin Smith, Duncan R. Nimlamool, Wutigri Pharmaceuticals (Basel) Article In the current study, we identified a mechanism of resveratrol (RES) underlying its anti-cancer properties against human ovarian adenocarcinoma SKOV-3 cells. We investigated its anti-proliferative and apoptosis-inducing effects in combination with cisplatin, using cell viability assay, flow cytometry, immunofluorescence study and Western blot analysis. We discovered that RES suppressed cancer cell proliferation and stimulated apoptosis, especially when combined with cisplatin. This compound also inhibited SKOV-3 cell survival, which may partly be due to its potential to inhibit protein kinase B (AKT) phosphorylation and induce the S-phase cell cycle arrest. RES in combination with cisplatin strongly induced cancer cell apoptosis through activating the caspase-dependent cascade, which was associated with its ability to stimulate nuclear phosphorylation of p38 mitogen-activated protein kinase (MAPK), well recognized to be involved in transducing environmental stress signals. RES-induced p38 phosphorylation was very specific, and the activation status of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) was not mainly affected. Taken together, our study provides accumulated evidence that RES represses proliferation and promotes apoptosis in SKOV-3 ovarian cancer cells through activating the p38 MAPK pathway. It is interesting that this active compound may be used as an effective agent to sensitize ovarian cancer to apoptosis induced by standard chemotherapies. MDPI 2023-05-17 /pmc/articles/PMC10220637/ /pubmed/37242538 http://dx.doi.org/10.3390/ph16050755 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hankittichai, Phateep
Thaklaewphan, Phatarawat
Wikan, Nitwara
Ruttanapattanakul, Jirapak
Potikanond, Saranyapin
Smith, Duncan R.
Nimlamool, Wutigri
Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT
title Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT
title_full Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT
title_fullStr Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT
title_full_unstemmed Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT
title_short Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT
title_sort resveratrol enhances cytotoxic effects of cisplatin by inducing cell cycle arrest and apoptosis in ovarian adenocarcinoma skov-3 cells through activating the p38 mapk and suppressing akt
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10220637/
https://www.ncbi.nlm.nih.gov/pubmed/37242538
http://dx.doi.org/10.3390/ph16050755
work_keys_str_mv AT hankittichaiphateep resveratrolenhancescytotoxiceffectsofcisplatinbyinducingcellcyclearrestandapoptosisinovarianadenocarcinomaskov3cellsthroughactivatingthep38mapkandsuppressingakt
AT thaklaewphanphatarawat resveratrolenhancescytotoxiceffectsofcisplatinbyinducingcellcyclearrestandapoptosisinovarianadenocarcinomaskov3cellsthroughactivatingthep38mapkandsuppressingakt
AT wikannitwara resveratrolenhancescytotoxiceffectsofcisplatinbyinducingcellcyclearrestandapoptosisinovarianadenocarcinomaskov3cellsthroughactivatingthep38mapkandsuppressingakt
AT ruttanapattanakuljirapak resveratrolenhancescytotoxiceffectsofcisplatinbyinducingcellcyclearrestandapoptosisinovarianadenocarcinomaskov3cellsthroughactivatingthep38mapkandsuppressingakt
AT potikanondsaranyapin resveratrolenhancescytotoxiceffectsofcisplatinbyinducingcellcyclearrestandapoptosisinovarianadenocarcinomaskov3cellsthroughactivatingthep38mapkandsuppressingakt
AT smithduncanr resveratrolenhancescytotoxiceffectsofcisplatinbyinducingcellcyclearrestandapoptosisinovarianadenocarcinomaskov3cellsthroughactivatingthep38mapkandsuppressingakt
AT nimlamoolwutigri resveratrolenhancescytotoxiceffectsofcisplatinbyinducingcellcyclearrestandapoptosisinovarianadenocarcinomaskov3cellsthroughactivatingthep38mapkandsuppressingakt