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Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway

Colorectal cancer (CRC) is one of the most common cancers worldwide, and approximately one-third of CRC patients present with metastatic disease. Periplocymarin (PPM), a cardiac glycoside isolated from Periploca sepium, is a latent anticancer compound. The purpose of this study was to explore the ef...

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Autores principales: Cheng, Yi, Wang, Guiying, Zhao, Lianmei, Dai, Suli, Han, Jing, Hu, Xuhua, Zhou, Chaoxi, Wang, Feifei, Ma, Hongqing, Li, Baokun, Meng, Zesong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8655334/
https://www.ncbi.nlm.nih.gov/pubmed/34900704
http://dx.doi.org/10.3389/fonc.2021.753598
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author Cheng, Yi
Wang, Guiying
Zhao, Lianmei
Dai, Suli
Han, Jing
Hu, Xuhua
Zhou, Chaoxi
Wang, Feifei
Ma, Hongqing
Li, Baokun
Meng, Zesong
author_facet Cheng, Yi
Wang, Guiying
Zhao, Lianmei
Dai, Suli
Han, Jing
Hu, Xuhua
Zhou, Chaoxi
Wang, Feifei
Ma, Hongqing
Li, Baokun
Meng, Zesong
author_sort Cheng, Yi
collection PubMed
description Colorectal cancer (CRC) is one of the most common cancers worldwide, and approximately one-third of CRC patients present with metastatic disease. Periplocymarin (PPM), a cardiac glycoside isolated from Periploca sepium, is a latent anticancer compound. The purpose of this study was to explore the effect of PPM on CRC cells. CRC cells were treated with PPM and cell viability was evaluated by CCK-8 assay. Flow cytometry and TUNEL staining were performed to assess cell cycle and apoptosis. Quantitative proteomics has been used to check the proteins differentially expressed by using tandem mass tag (TMT) labeling and liquid chromatography–tandem mass spectrometry. Bioinformatic analysis was undertaken to identify the biological processes that these differentially expressed proteins are involved in. Gene expression was analyzed by western blotting. The effect of PPM in vivo was primarily checked in a subcutaneous xenograft mouse model of CRC, and the gene expression of tumor was checked by histochemistry staining. PPM could inhibit the proliferation of CRC cells in a dose-dependent manner, induce cell apoptosis and promote G0/G1 cell cycle arrest. A total of 539 proteins were identified differentially expressed following PPM treatment, where among those there were 286 genes upregulated and 293 downregulated. PPM treatment caused a pro-apoptosis gene expression profile both in vivo and in vitro, and impaired PI3K/AKT signaling pathway might be involved. In addition, PPM treatment caused less detrimental effects on blood cell, hepatic and renal function in mice, and the anti-cancer effect was found exaggerated by PPM+5-FU combination treatment. PPM may perform anti-CRC effects by promoting cell apoptosis and this might be achieved by targeting PI3K/AKT pathway. PPM might be a safe and promising anti-cancer drug that needs to be further studied.
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spelling pubmed-86553342021-12-10 Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway Cheng, Yi Wang, Guiying Zhao, Lianmei Dai, Suli Han, Jing Hu, Xuhua Zhou, Chaoxi Wang, Feifei Ma, Hongqing Li, Baokun Meng, Zesong Front Oncol Oncology Colorectal cancer (CRC) is one of the most common cancers worldwide, and approximately one-third of CRC patients present with metastatic disease. Periplocymarin (PPM), a cardiac glycoside isolated from Periploca sepium, is a latent anticancer compound. The purpose of this study was to explore the effect of PPM on CRC cells. CRC cells were treated with PPM and cell viability was evaluated by CCK-8 assay. Flow cytometry and TUNEL staining were performed to assess cell cycle and apoptosis. Quantitative proteomics has been used to check the proteins differentially expressed by using tandem mass tag (TMT) labeling and liquid chromatography–tandem mass spectrometry. Bioinformatic analysis was undertaken to identify the biological processes that these differentially expressed proteins are involved in. Gene expression was analyzed by western blotting. The effect of PPM in vivo was primarily checked in a subcutaneous xenograft mouse model of CRC, and the gene expression of tumor was checked by histochemistry staining. PPM could inhibit the proliferation of CRC cells in a dose-dependent manner, induce cell apoptosis and promote G0/G1 cell cycle arrest. A total of 539 proteins were identified differentially expressed following PPM treatment, where among those there were 286 genes upregulated and 293 downregulated. PPM treatment caused a pro-apoptosis gene expression profile both in vivo and in vitro, and impaired PI3K/AKT signaling pathway might be involved. In addition, PPM treatment caused less detrimental effects on blood cell, hepatic and renal function in mice, and the anti-cancer effect was found exaggerated by PPM+5-FU combination treatment. PPM may perform anti-CRC effects by promoting cell apoptosis and this might be achieved by targeting PI3K/AKT pathway. PPM might be a safe and promising anti-cancer drug that needs to be further studied. Frontiers Media S.A. 2021-11-25 /pmc/articles/PMC8655334/ /pubmed/34900704 http://dx.doi.org/10.3389/fonc.2021.753598 Text en Copyright © 2021 Cheng, Wang, Zhao, Dai, Han, Hu, Zhou, Wang, Ma, Li and Meng 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
Cheng, Yi
Wang, Guiying
Zhao, Lianmei
Dai, Suli
Han, Jing
Hu, Xuhua
Zhou, Chaoxi
Wang, Feifei
Ma, Hongqing
Li, Baokun
Meng, Zesong
Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway
title Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway
title_full Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway
title_fullStr Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway
title_full_unstemmed Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway
title_short Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway
title_sort periplocymarin induced colorectal cancer cells apoptosis via impairing pi3k/akt pathway
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8655334/
https://www.ncbi.nlm.nih.gov/pubmed/34900704
http://dx.doi.org/10.3389/fonc.2021.753598
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