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Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway

Cinobufacini injection (CI), an aqueous extract of Cutis Bufonis, is clinically used for cancer therapy in China, but its molecular mechanism for the treatment of osteosarcoma (OS) remains unclear. We constructed U2OS ectopic subcutaneous tumor model to verify the anti-OS effect of CI in vivo. Meanw...

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Autores principales: Chen, Yuru, Wang, Yanyan, Zhai, Yu, Yuan, Ye, Wang, Junhong, Jin, Yajing, Dang, Lingling, Song, Liming, Chen, Changbao, Wang, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10063998/
https://www.ncbi.nlm.nih.gov/pubmed/37006999
http://dx.doi.org/10.3389/fphar.2023.1081363
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author Chen, Yuru
Wang, Yanyan
Zhai, Yu
Yuan, Ye
Wang, Junhong
Jin, Yajing
Dang, Lingling
Song, Liming
Chen, Changbao
Wang, Yu
author_facet Chen, Yuru
Wang, Yanyan
Zhai, Yu
Yuan, Ye
Wang, Junhong
Jin, Yajing
Dang, Lingling
Song, Liming
Chen, Changbao
Wang, Yu
author_sort Chen, Yuru
collection PubMed
description Cinobufacini injection (CI), an aqueous extract of Cutis Bufonis, is clinically used for cancer therapy in China, but its molecular mechanism for the treatment of osteosarcoma (OS) remains unclear. We constructed U2OS ectopic subcutaneous tumor model to verify the anti-OS effect of CI in vivo. Meanwhile, cell proliferation of U2OS and MG63 cells was monitored in vitro using the CCK-8 assay, colony formation and morphological changes. Cell cycle arrest and apoptosis were detected by flow cytometry and western blot, which showed that CI significantly inhibited proliferation, induced cell cycle arrest and apoptosis in human OS cells. The further RNA-seq results identified that the Hippo signaling pathway was involved in the anti-OS effect of CI. YAP/TAZ are two major components of the Hippo pathway in breast cancer and are positively regulated by prolyl isomerase PIN1, we assessed their role in OS using both clinicopathological sections and western blots. CI also inhibited PIN1 enzyme activity in a dose-dependent manner, which resulted in impaired PIN1, YAP, and TAZ expression in vitro and in vivo. Additionally, 15 potential compounds of CI were found to occupy the PIN1 kinase domain and inhibit its activity. In summary, CI plays an anti-OS role by down-regulating the PIN1-YAP/TAZ pathway.
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spelling pubmed-100639982023-04-01 Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway Chen, Yuru Wang, Yanyan Zhai, Yu Yuan, Ye Wang, Junhong Jin, Yajing Dang, Lingling Song, Liming Chen, Changbao Wang, Yu Front Pharmacol Pharmacology Cinobufacini injection (CI), an aqueous extract of Cutis Bufonis, is clinically used for cancer therapy in China, but its molecular mechanism for the treatment of osteosarcoma (OS) remains unclear. We constructed U2OS ectopic subcutaneous tumor model to verify the anti-OS effect of CI in vivo. Meanwhile, cell proliferation of U2OS and MG63 cells was monitored in vitro using the CCK-8 assay, colony formation and morphological changes. Cell cycle arrest and apoptosis were detected by flow cytometry and western blot, which showed that CI significantly inhibited proliferation, induced cell cycle arrest and apoptosis in human OS cells. The further RNA-seq results identified that the Hippo signaling pathway was involved in the anti-OS effect of CI. YAP/TAZ are two major components of the Hippo pathway in breast cancer and are positively regulated by prolyl isomerase PIN1, we assessed their role in OS using both clinicopathological sections and western blots. CI also inhibited PIN1 enzyme activity in a dose-dependent manner, which resulted in impaired PIN1, YAP, and TAZ expression in vitro and in vivo. Additionally, 15 potential compounds of CI were found to occupy the PIN1 kinase domain and inhibit its activity. In summary, CI plays an anti-OS role by down-regulating the PIN1-YAP/TAZ pathway. Frontiers Media S.A. 2023-03-17 /pmc/articles/PMC10063998/ /pubmed/37006999 http://dx.doi.org/10.3389/fphar.2023.1081363 Text en Copyright © 2023 Chen, Wang, Zhai, Yuan, Wang, Jin, Dang, Song, Chen and Wang. 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 Pharmacology
Chen, Yuru
Wang, Yanyan
Zhai, Yu
Yuan, Ye
Wang, Junhong
Jin, Yajing
Dang, Lingling
Song, Liming
Chen, Changbao
Wang, Yu
Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway
title Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway
title_full Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway
title_fullStr Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway
title_full_unstemmed Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway
title_short Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway
title_sort cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting pin1-yap/taz signaling pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10063998/
https://www.ncbi.nlm.nih.gov/pubmed/37006999
http://dx.doi.org/10.3389/fphar.2023.1081363
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