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Ginsenoside Rg5 Sensitizes Paclitaxel—Resistant Human Cervical-Adeno-Carcinoma Cells to Paclitaxel—And Enhances the Anticancer Effect of Paclitaxel

In cervical cancer chemotherapy, paclitaxel (PTX) chemoresistance has become a major difficulty, and it also affects the survival rate of numerous tumor patients. Thus, for the reversal of chemoresistance, it is imperative to develop combinatory drugs with petite or almost no side effects to sensiti...

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Autores principales: Ramesh, Janani, Thilakan, Rejani Chalikkaran, Gopalakrishnan, Raja Mohan, Vijayapoopathi, Singaravel, Dorschel, Arianna, Venugopal, Bhuvarahamurthy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316462/
https://www.ncbi.nlm.nih.gov/pubmed/35885925
http://dx.doi.org/10.3390/genes13071142
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author Ramesh, Janani
Thilakan, Rejani Chalikkaran
Gopalakrishnan, Raja Mohan
Vijayapoopathi, Singaravel
Dorschel, Arianna
Venugopal, Bhuvarahamurthy
author_facet Ramesh, Janani
Thilakan, Rejani Chalikkaran
Gopalakrishnan, Raja Mohan
Vijayapoopathi, Singaravel
Dorschel, Arianna
Venugopal, Bhuvarahamurthy
author_sort Ramesh, Janani
collection PubMed
description In cervical cancer chemotherapy, paclitaxel (PTX) chemoresistance has become a major difficulty, and it also affects the survival rate of numerous tumor patients. Thus, for the reversal of chemoresistance, it is imperative to develop combinatory drugs with petite or almost no side effects to sensitize cells to paclitaxel. Ginsenoside Rg5 (GRg5) may act as a chemosensitizer by reversing multidrug resistance. The present study aimed to determine the potential of GRg5 as a chemosensitizer in PTX-resistant human cervical adeno-carcinoma cell lines (HeLa cells). MTT assay was carried out to assess whether GRg5 can potentiate the cytotoxic effect of PTX in PTX- resistant HeLa cells; using flow cytometry-based annexin V-FITC assay, cellular apoptosis was analyzed; the rate of expression of the cell cycle, apoptosis and major cell-survival-signaling-related genes and its proteins were examined using RT-PCR and Western blotting technique. We found increased mRNA expression of Bak, Bax, Bid, and PUMA genes, whereas the mRNA expression of Bcl2, Bcl-XL, c-IAP-1, and MCL-1 were low; GRg5 combination triggered the efficacy of paclitaxel, which led to increased expression of Bax with an enhanced caspase-9/-3 activation, and apoptosis. Moreover, the study supports GRg5 as an inhibitor of two key signaling proteins, Akt and NF-κB, by which GRg5 augments the susceptibility of cervical cancer cells to PTX chemotherapy. GRg5 drastically potentiated the antiproliferative and pro-apoptotic activity of paclitaxel in PTX-resistant human cervical cancer cells in a synergistic mode. Moreover, in the clinical context, combining paclitaxel with GRg5 may prove to be a new approach for enhancing the efficacy of the paclitaxel.
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spelling pubmed-93164622022-07-27 Ginsenoside Rg5 Sensitizes Paclitaxel—Resistant Human Cervical-Adeno-Carcinoma Cells to Paclitaxel—And Enhances the Anticancer Effect of Paclitaxel Ramesh, Janani Thilakan, Rejani Chalikkaran Gopalakrishnan, Raja Mohan Vijayapoopathi, Singaravel Dorschel, Arianna Venugopal, Bhuvarahamurthy Genes (Basel) Article In cervical cancer chemotherapy, paclitaxel (PTX) chemoresistance has become a major difficulty, and it also affects the survival rate of numerous tumor patients. Thus, for the reversal of chemoresistance, it is imperative to develop combinatory drugs with petite or almost no side effects to sensitize cells to paclitaxel. Ginsenoside Rg5 (GRg5) may act as a chemosensitizer by reversing multidrug resistance. The present study aimed to determine the potential of GRg5 as a chemosensitizer in PTX-resistant human cervical adeno-carcinoma cell lines (HeLa cells). MTT assay was carried out to assess whether GRg5 can potentiate the cytotoxic effect of PTX in PTX- resistant HeLa cells; using flow cytometry-based annexin V-FITC assay, cellular apoptosis was analyzed; the rate of expression of the cell cycle, apoptosis and major cell-survival-signaling-related genes and its proteins were examined using RT-PCR and Western blotting technique. We found increased mRNA expression of Bak, Bax, Bid, and PUMA genes, whereas the mRNA expression of Bcl2, Bcl-XL, c-IAP-1, and MCL-1 were low; GRg5 combination triggered the efficacy of paclitaxel, which led to increased expression of Bax with an enhanced caspase-9/-3 activation, and apoptosis. Moreover, the study supports GRg5 as an inhibitor of two key signaling proteins, Akt and NF-κB, by which GRg5 augments the susceptibility of cervical cancer cells to PTX chemotherapy. GRg5 drastically potentiated the antiproliferative and pro-apoptotic activity of paclitaxel in PTX-resistant human cervical cancer cells in a synergistic mode. Moreover, in the clinical context, combining paclitaxel with GRg5 may prove to be a new approach for enhancing the efficacy of the paclitaxel. MDPI 2022-06-24 /pmc/articles/PMC9316462/ /pubmed/35885925 http://dx.doi.org/10.3390/genes13071142 Text en © 2022 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
Ramesh, Janani
Thilakan, Rejani Chalikkaran
Gopalakrishnan, Raja Mohan
Vijayapoopathi, Singaravel
Dorschel, Arianna
Venugopal, Bhuvarahamurthy
Ginsenoside Rg5 Sensitizes Paclitaxel—Resistant Human Cervical-Adeno-Carcinoma Cells to Paclitaxel—And Enhances the Anticancer Effect of Paclitaxel
title Ginsenoside Rg5 Sensitizes Paclitaxel—Resistant Human Cervical-Adeno-Carcinoma Cells to Paclitaxel—And Enhances the Anticancer Effect of Paclitaxel
title_full Ginsenoside Rg5 Sensitizes Paclitaxel—Resistant Human Cervical-Adeno-Carcinoma Cells to Paclitaxel—And Enhances the Anticancer Effect of Paclitaxel
title_fullStr Ginsenoside Rg5 Sensitizes Paclitaxel—Resistant Human Cervical-Adeno-Carcinoma Cells to Paclitaxel—And Enhances the Anticancer Effect of Paclitaxel
title_full_unstemmed Ginsenoside Rg5 Sensitizes Paclitaxel—Resistant Human Cervical-Adeno-Carcinoma Cells to Paclitaxel—And Enhances the Anticancer Effect of Paclitaxel
title_short Ginsenoside Rg5 Sensitizes Paclitaxel—Resistant Human Cervical-Adeno-Carcinoma Cells to Paclitaxel—And Enhances the Anticancer Effect of Paclitaxel
title_sort ginsenoside rg5 sensitizes paclitaxel—resistant human cervical-adeno-carcinoma cells to paclitaxel—and enhances the anticancer effect of paclitaxel
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316462/
https://www.ncbi.nlm.nih.gov/pubmed/35885925
http://dx.doi.org/10.3390/genes13071142
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