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A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs
Background. Many anti-cancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (Compound A) and 3-[(1E)-2-(4-hydroxyph...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10386476/ https://www.ncbi.nlm.nih.gov/pubmed/37505064 http://dx.doi.org/10.3390/medicines10070043 |
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author | Abe, Tomoyuki Sakagami, Hiroshi Amano, Shigeru Uota, Shin Bandow, Kenjiro Uesawa, Yoshihiro U, Shiori Shibata, Hiroki Takemura, Yuri Kimura, Yu Takao, Koichi Sugita, Yoshiaki Sato, Akira Tanuma, Sei-ichi Takeshima, Hiroshi |
author_facet | Abe, Tomoyuki Sakagami, Hiroshi Amano, Shigeru Uota, Shin Bandow, Kenjiro Uesawa, Yoshihiro U, Shiori Shibata, Hiroki Takemura, Yuri Kimura, Yu Takao, Koichi Sugita, Yoshiaki Sato, Akira Tanuma, Sei-ichi Takeshima, Hiroshi |
author_sort | Abe, Tomoyuki |
collection | PubMed |
description | Background. Many anti-cancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (Compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (Compound B), showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds in comparison with four popular anti-cancer drugs. Methods: Tumor-specificity (TS(M), TS(E), TS(N)) was evaluated as the ratio of mean CC(50) for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one order of magnitude higher TS(M) than newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TS(M), but two orders of magnitude lower TS(E) than Compounds A and B. Compounds A and B showed higher TS(M), TS(E,) and TS(N) values than doxorubicin, 5-FU, and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that Compounds A and B may inhibit the signaling pathway of estrogen-related receptors. |
format | Online Article Text |
id | pubmed-10386476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103864762023-07-30 A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs Abe, Tomoyuki Sakagami, Hiroshi Amano, Shigeru Uota, Shin Bandow, Kenjiro Uesawa, Yoshihiro U, Shiori Shibata, Hiroki Takemura, Yuri Kimura, Yu Takao, Koichi Sugita, Yoshiaki Sato, Akira Tanuma, Sei-ichi Takeshima, Hiroshi Medicines (Basel) Article Background. Many anti-cancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (Compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (Compound B), showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds in comparison with four popular anti-cancer drugs. Methods: Tumor-specificity (TS(M), TS(E), TS(N)) was evaluated as the ratio of mean CC(50) for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one order of magnitude higher TS(M) than newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TS(M), but two orders of magnitude lower TS(E) than Compounds A and B. Compounds A and B showed higher TS(M), TS(E,) and TS(N) values than doxorubicin, 5-FU, and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that Compounds A and B may inhibit the signaling pathway of estrogen-related receptors. MDPI 2023-07-14 /pmc/articles/PMC10386476/ /pubmed/37505064 http://dx.doi.org/10.3390/medicines10070043 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 Abe, Tomoyuki Sakagami, Hiroshi Amano, Shigeru Uota, Shin Bandow, Kenjiro Uesawa, Yoshihiro U, Shiori Shibata, Hiroki Takemura, Yuri Kimura, Yu Takao, Koichi Sugita, Yoshiaki Sato, Akira Tanuma, Sei-ichi Takeshima, Hiroshi A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs |
title | A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs |
title_full | A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs |
title_fullStr | A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs |
title_full_unstemmed | A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs |
title_short | A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs |
title_sort | comparative study of tumor-specificity and neurotoxicity between 3-styrylchromones and anti-cancer drugs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10386476/ https://www.ncbi.nlm.nih.gov/pubmed/37505064 http://dx.doi.org/10.3390/medicines10070043 |
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