Cargando…

Combination Treatment of Withalongolide a Triacetate with Cisplatin Induces Apoptosis by Targeting Translational Initiation, Migration, and Epithelial to Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma

Treatment regimens for head and neck squamous cell carcinoma (HNSCC) typically include cisplatin and radiotherapy and are limited by toxicities. We have identified naturally derived withalongolide A triacetate (WGA-TA) from Physalis longifolia as a lead compound for targeting HNSCC. We hypothesized...

Descripción completa

Detalles Bibliográficos
Autores principales: Subramanian, Chitra, Spielbauer, Katie K., Pearce, Robin, Kovatch, Kevin J., Prince, Mark E., Timmermann, Barbara N., Cohen, Mark S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782118/
https://www.ncbi.nlm.nih.gov/pubmed/36558560
http://dx.doi.org/10.3390/nu14245398
_version_ 1784857263310110720
author Subramanian, Chitra
Spielbauer, Katie K.
Pearce, Robin
Kovatch, Kevin J.
Prince, Mark E.
Timmermann, Barbara N.
Cohen, Mark S.
author_facet Subramanian, Chitra
Spielbauer, Katie K.
Pearce, Robin
Kovatch, Kevin J.
Prince, Mark E.
Timmermann, Barbara N.
Cohen, Mark S.
author_sort Subramanian, Chitra
collection PubMed
description Treatment regimens for head and neck squamous cell carcinoma (HNSCC) typically include cisplatin and radiotherapy and are limited by toxicities. We have identified naturally derived withalongolide A triacetate (WGA-TA) from Physalis longifolia as a lead compound for targeting HNSCC. We hypothesized that combining WGA-TA with cisplatin may allow for lower, less toxic cisplatin doses. HNSCC cell lines were treated with WGA-TA and cisplatin. After treatment with the drugs, the cell viability was determined by MTS assay. The combination index was calculated using CompuSyn. The expression of proteins involved in the targeting of translational initiation complex, epithelial to mesenchymal transition (EMT), and apoptosis were measured by western blot. Invasion and migration were measured using the Boyden-chamber assay. Treatment of MDA-1986 and UMSCC-22B cell lines with either WGA-TA or cisplatin alone for 72 h resulted in a dose dependent decrease in cell viability. Cisplatin in combination with WGA-TA resulted in significant synergistic cell death starting from 1.25 μM cisplatin. Combination treatment with WGA-TA resulted in lower cisplatin dosing while maintaining the downregulation of translational initiation complex proteins, the induction of apoptosis, and the blockade of migration, invasion, and EMT transition. These results suggest that combining a low concentration of cisplatin with WGA-TA may provide a safer, more effective therapeutic option for HNSCC that warrants translational validation.
format Online
Article
Text
id pubmed-9782118
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-97821182022-12-24 Combination Treatment of Withalongolide a Triacetate with Cisplatin Induces Apoptosis by Targeting Translational Initiation, Migration, and Epithelial to Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma Subramanian, Chitra Spielbauer, Katie K. Pearce, Robin Kovatch, Kevin J. Prince, Mark E. Timmermann, Barbara N. Cohen, Mark S. Nutrients Article Treatment regimens for head and neck squamous cell carcinoma (HNSCC) typically include cisplatin and radiotherapy and are limited by toxicities. We have identified naturally derived withalongolide A triacetate (WGA-TA) from Physalis longifolia as a lead compound for targeting HNSCC. We hypothesized that combining WGA-TA with cisplatin may allow for lower, less toxic cisplatin doses. HNSCC cell lines were treated with WGA-TA and cisplatin. After treatment with the drugs, the cell viability was determined by MTS assay. The combination index was calculated using CompuSyn. The expression of proteins involved in the targeting of translational initiation complex, epithelial to mesenchymal transition (EMT), and apoptosis were measured by western blot. Invasion and migration were measured using the Boyden-chamber assay. Treatment of MDA-1986 and UMSCC-22B cell lines with either WGA-TA or cisplatin alone for 72 h resulted in a dose dependent decrease in cell viability. Cisplatin in combination with WGA-TA resulted in significant synergistic cell death starting from 1.25 μM cisplatin. Combination treatment with WGA-TA resulted in lower cisplatin dosing while maintaining the downregulation of translational initiation complex proteins, the induction of apoptosis, and the blockade of migration, invasion, and EMT transition. These results suggest that combining a low concentration of cisplatin with WGA-TA may provide a safer, more effective therapeutic option for HNSCC that warrants translational validation. MDPI 2022-12-19 /pmc/articles/PMC9782118/ /pubmed/36558560 http://dx.doi.org/10.3390/nu14245398 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
Subramanian, Chitra
Spielbauer, Katie K.
Pearce, Robin
Kovatch, Kevin J.
Prince, Mark E.
Timmermann, Barbara N.
Cohen, Mark S.
Combination Treatment of Withalongolide a Triacetate with Cisplatin Induces Apoptosis by Targeting Translational Initiation, Migration, and Epithelial to Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma
title Combination Treatment of Withalongolide a Triacetate with Cisplatin Induces Apoptosis by Targeting Translational Initiation, Migration, and Epithelial to Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma
title_full Combination Treatment of Withalongolide a Triacetate with Cisplatin Induces Apoptosis by Targeting Translational Initiation, Migration, and Epithelial to Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma
title_fullStr Combination Treatment of Withalongolide a Triacetate with Cisplatin Induces Apoptosis by Targeting Translational Initiation, Migration, and Epithelial to Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma
title_full_unstemmed Combination Treatment of Withalongolide a Triacetate with Cisplatin Induces Apoptosis by Targeting Translational Initiation, Migration, and Epithelial to Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma
title_short Combination Treatment of Withalongolide a Triacetate with Cisplatin Induces Apoptosis by Targeting Translational Initiation, Migration, and Epithelial to Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma
title_sort combination treatment of withalongolide a triacetate with cisplatin induces apoptosis by targeting translational initiation, migration, and epithelial to mesenchymal transition in head and neck squamous cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782118/
https://www.ncbi.nlm.nih.gov/pubmed/36558560
http://dx.doi.org/10.3390/nu14245398
work_keys_str_mv AT subramanianchitra combinationtreatmentofwithalongolideatriacetatewithcisplatininducesapoptosisbytargetingtranslationalinitiationmigrationandepithelialtomesenchymaltransitioninheadandnecksquamouscellcarcinoma
AT spielbauerkatiek combinationtreatmentofwithalongolideatriacetatewithcisplatininducesapoptosisbytargetingtranslationalinitiationmigrationandepithelialtomesenchymaltransitioninheadandnecksquamouscellcarcinoma
AT pearcerobin combinationtreatmentofwithalongolideatriacetatewithcisplatininducesapoptosisbytargetingtranslationalinitiationmigrationandepithelialtomesenchymaltransitioninheadandnecksquamouscellcarcinoma
AT kovatchkevinj combinationtreatmentofwithalongolideatriacetatewithcisplatininducesapoptosisbytargetingtranslationalinitiationmigrationandepithelialtomesenchymaltransitioninheadandnecksquamouscellcarcinoma
AT princemarke combinationtreatmentofwithalongolideatriacetatewithcisplatininducesapoptosisbytargetingtranslationalinitiationmigrationandepithelialtomesenchymaltransitioninheadandnecksquamouscellcarcinoma
AT timmermannbarbaran combinationtreatmentofwithalongolideatriacetatewithcisplatininducesapoptosisbytargetingtranslationalinitiationmigrationandepithelialtomesenchymaltransitioninheadandnecksquamouscellcarcinoma
AT cohenmarks combinationtreatmentofwithalongolideatriacetatewithcisplatininducesapoptosisbytargetingtranslationalinitiationmigrationandepithelialtomesenchymaltransitioninheadandnecksquamouscellcarcinoma