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Z-Ligustilide Induces c-Myc-Dependent Apoptosis via Activation of ER-Stress Signaling in Hypoxic Oral Cancer Cells

Z-ligustilide (or ligustilide) is found in Angelica sinensis (Oliv.) Diels and may exert potential benefits in cancer treatment. Previous research has reported that ligustilide has anti-cancer effects on several types of cancer cells. However, studies of ligustilide on oral cancer cells have not bee...

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Autores principales: Hsu, Ren-Jun, Peng, Kui-Yuan, Hsu, Wen-Lin, Chen, Yu-Tang, Liu, Dai-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043595/
https://www.ncbi.nlm.nih.gov/pubmed/35494068
http://dx.doi.org/10.3389/fonc.2022.824043
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author Hsu, Ren-Jun
Peng, Kui-Yuan
Hsu, Wen-Lin
Chen, Yu-Tang
Liu, Dai-Wei
author_facet Hsu, Ren-Jun
Peng, Kui-Yuan
Hsu, Wen-Lin
Chen, Yu-Tang
Liu, Dai-Wei
author_sort Hsu, Ren-Jun
collection PubMed
description Z-ligustilide (or ligustilide) is found in Angelica sinensis (Oliv.) Diels and may exert potential benefits in cancer treatment. Previous research has reported that ligustilide has anti-cancer effects on several types of cancer cells. However, studies of ligustilide on oral cancer cells have not been reported, especially under hypoxic conditions. This study focuses on the molecular mechanism of ligustilide-induced apoptosis in hypoxic oral cancer cells. We found that in hypoxic TW2.6 cells, ligustilide inhibited cell migration and induced caspase-dependent apoptosis. Accumulation of c-Myc accompanied by BH3-only members suggests that ligustilide may induce c-Myc-dependent apoptosis. In addition, we reported that ligustilide has an effect on ER-stress signaling. By using inhibitors of c-Myc, IRE1α, and ER-stress inhibitors, we found that cell morphologies or cell viability were rescued to some degree. Moreover, ligustilide is able to increase the expression of γ-H2AX and enhance the occurrence of DNA damage in oral cancer cells after radiation treatment. This result suggests that ligustilide has potential as a radiation sensitizer. Altogether, we propose that ligustilide may induce c-Myc-dependent apoptosis via ER-stress signaling in hypoxic oral cancer cells.
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spelling pubmed-90435952022-04-28 Z-Ligustilide Induces c-Myc-Dependent Apoptosis via Activation of ER-Stress Signaling in Hypoxic Oral Cancer Cells Hsu, Ren-Jun Peng, Kui-Yuan Hsu, Wen-Lin Chen, Yu-Tang Liu, Dai-Wei Front Oncol Oncology Z-ligustilide (or ligustilide) is found in Angelica sinensis (Oliv.) Diels and may exert potential benefits in cancer treatment. Previous research has reported that ligustilide has anti-cancer effects on several types of cancer cells. However, studies of ligustilide on oral cancer cells have not been reported, especially under hypoxic conditions. This study focuses on the molecular mechanism of ligustilide-induced apoptosis in hypoxic oral cancer cells. We found that in hypoxic TW2.6 cells, ligustilide inhibited cell migration and induced caspase-dependent apoptosis. Accumulation of c-Myc accompanied by BH3-only members suggests that ligustilide may induce c-Myc-dependent apoptosis. In addition, we reported that ligustilide has an effect on ER-stress signaling. By using inhibitors of c-Myc, IRE1α, and ER-stress inhibitors, we found that cell morphologies or cell viability were rescued to some degree. Moreover, ligustilide is able to increase the expression of γ-H2AX and enhance the occurrence of DNA damage in oral cancer cells after radiation treatment. This result suggests that ligustilide has potential as a radiation sensitizer. Altogether, we propose that ligustilide may induce c-Myc-dependent apoptosis via ER-stress signaling in hypoxic oral cancer cells. Frontiers Media S.A. 2022-04-13 /pmc/articles/PMC9043595/ /pubmed/35494068 http://dx.doi.org/10.3389/fonc.2022.824043 Text en Copyright © 2022 Hsu, Peng, Hsu, Chen and Liu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Hsu, Ren-Jun
Peng, Kui-Yuan
Hsu, Wen-Lin
Chen, Yu-Tang
Liu, Dai-Wei
Z-Ligustilide Induces c-Myc-Dependent Apoptosis via Activation of ER-Stress Signaling in Hypoxic Oral Cancer Cells
title Z-Ligustilide Induces c-Myc-Dependent Apoptosis via Activation of ER-Stress Signaling in Hypoxic Oral Cancer Cells
title_full Z-Ligustilide Induces c-Myc-Dependent Apoptosis via Activation of ER-Stress Signaling in Hypoxic Oral Cancer Cells
title_fullStr Z-Ligustilide Induces c-Myc-Dependent Apoptosis via Activation of ER-Stress Signaling in Hypoxic Oral Cancer Cells
title_full_unstemmed Z-Ligustilide Induces c-Myc-Dependent Apoptosis via Activation of ER-Stress Signaling in Hypoxic Oral Cancer Cells
title_short Z-Ligustilide Induces c-Myc-Dependent Apoptosis via Activation of ER-Stress Signaling in Hypoxic Oral Cancer Cells
title_sort z-ligustilide induces c-myc-dependent apoptosis via activation of er-stress signaling in hypoxic oral cancer cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043595/
https://www.ncbi.nlm.nih.gov/pubmed/35494068
http://dx.doi.org/10.3389/fonc.2022.824043
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