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:	Yi Cheng, Guiying Wang, Lianmei Zhao, Suli Dai, Jing Han, Xuhua Hu, Chaoxi Zhou, Feifei Wang, Hongqing Ma, Baokun Li, Zesong Meng
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	colorectal cancer periplocymarin apoptosis IRS1 PI3K/AKT pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a7c05fd1c0b24ce483a85065f5353ac9
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spelling	oai:doaj.org-article:a7c05fd1c0b24ce483a85065f5353ac92021-11-30T23:33:56ZPeriplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway2234-943X10.3389/fonc.2021.753598https://doaj.org/article/a7c05fd1c0b24ce483a85065f5353ac92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.753598/fullhttps://doaj.org/toc/2234-943XColorectal 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.Yi ChengGuiying WangGuiying WangLianmei ZhaoSuli DaiJing HanXuhua HuChaoxi ZhouFeifei WangHongqing MaBaokun LiZesong MengFrontiers Media S.A.articlecolorectal cancerperiplocymarinapoptosisIRS1PI3K/AKT pathwayNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer periplocymarin apoptosis IRS1 PI3K/AKT pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	colorectal cancer periplocymarin apoptosis IRS1 PI3K/AKT pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yi Cheng Guiying Wang Guiying Wang Lianmei Zhao Suli Dai Jing Han Xuhua Hu Chaoxi Zhou Feifei Wang Hongqing Ma Baokun Li Zesong Meng Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway
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.
format	article
author	Yi Cheng Guiying Wang Guiying Wang Lianmei Zhao Suli Dai Jing Han Xuhua Hu Chaoxi Zhou Feifei Wang Hongqing Ma Baokun Li Zesong Meng
author_facet	Yi Cheng Guiying Wang Guiying Wang Lianmei Zhao Suli Dai Jing Han Xuhua Hu Chaoxi Zhou Feifei Wang Hongqing Ma Baokun Li Zesong Meng
author_sort	Yi Cheng
title	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_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_sort	periplocymarin induced colorectal cancer cells apoptosis via impairing pi3k/akt pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a7c05fd1c0b24ce483a85065f5353ac9
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Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway

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