Potent antitumor activity of a glutamyltransferase-derived peptide via an activation of oncosis pathway

Abstract Hepatocellular carcinoma (HCC) still presents poor prognosis with high mortality rate, despite of the improvement in the management. The challenge for precision treatment was due to the fact that little targeted therapeutics are available for HCC. Recent studies show that metabolic and circ...

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Autores principales:	Cheng Fang, Wenhui Li, Ruozhe Yin, Donglie Zhu, Xing Liu, Huihui Wu, Qingqiang Wang, Wenwen Wang, Quan Bai, Biliang Chen, Xuebiao Yao, Yong Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2ff30b6042fd422ea9764d949ca96111
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spelling	oai:doaj.org-article:2ff30b6042fd422ea9764d949ca961112021-12-02T15:08:22ZPotent antitumor activity of a glutamyltransferase-derived peptide via an activation of oncosis pathway10.1038/s41598-021-93055-52045-2322https://doaj.org/article/2ff30b6042fd422ea9764d949ca961112021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93055-5https://doaj.org/toc/2045-2322Abstract Hepatocellular carcinoma (HCC) still presents poor prognosis with high mortality rate, despite of the improvement in the management. The challenge for precision treatment was due to the fact that little targeted therapeutics are available for HCC. Recent studies show that metabolic and circulating peptides serve as endogenous switches for correcting aberrant cellular plasticity. Here we explored the antitumor activity of low molecular components in human umbilical serum and identified a high abundance peptide VI-13 by peptidome analysis, which was recognized as the part of glutamyltransferase signal peptide. We modified VI-13 by inserting four arginines and obtained an analog peptide VI-17 to improve its solubility. Our analyses showed that the peptide VI-17 induced rapid context-dependent cell death, and exhibited a higher sensitivity on hepatoma cells, which is attenuated by polyethylene glycol but not necrotic inhibitors such as z-VAD-fmk or necrostatin-1. Morphologically, VI-17 induced cell swelling, blebbing and membrane rupture with release of cellular ATP and LDH into extracellular media, which is hallmark of oncotic process. Mechanistically, VI-17 induced cell membrane pore formation, degradation of α-tubulin via influx of calcium ion. These results indicated that the novel peptide VI-17 induced oncosis in HCC cells, which could serve as a promising lead for development of therapeutic intervention of HCC.Cheng FangWenhui LiRuozhe YinDonglie ZhuXing LiuHuihui WuQingqiang WangWenwen WangQuan BaiBiliang ChenXuebiao YaoYong ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cheng Fang Wenhui Li Ruozhe Yin Donglie Zhu Xing Liu Huihui Wu Qingqiang Wang Wenwen Wang Quan Bai Biliang Chen Xuebiao Yao Yong Chen Potent antitumor activity of a glutamyltransferase-derived peptide via an activation of oncosis pathway
description	Abstract Hepatocellular carcinoma (HCC) still presents poor prognosis with high mortality rate, despite of the improvement in the management. The challenge for precision treatment was due to the fact that little targeted therapeutics are available for HCC. Recent studies show that metabolic and circulating peptides serve as endogenous switches for correcting aberrant cellular plasticity. Here we explored the antitumor activity of low molecular components in human umbilical serum and identified a high abundance peptide VI-13 by peptidome analysis, which was recognized as the part of glutamyltransferase signal peptide. We modified VI-13 by inserting four arginines and obtained an analog peptide VI-17 to improve its solubility. Our analyses showed that the peptide VI-17 induced rapid context-dependent cell death, and exhibited a higher sensitivity on hepatoma cells, which is attenuated by polyethylene glycol but not necrotic inhibitors such as z-VAD-fmk or necrostatin-1. Morphologically, VI-17 induced cell swelling, blebbing and membrane rupture with release of cellular ATP and LDH into extracellular media, which is hallmark of oncotic process. Mechanistically, VI-17 induced cell membrane pore formation, degradation of α-tubulin via influx of calcium ion. These results indicated that the novel peptide VI-17 induced oncosis in HCC cells, which could serve as a promising lead for development of therapeutic intervention of HCC.
format	article
author	Cheng Fang Wenhui Li Ruozhe Yin Donglie Zhu Xing Liu Huihui Wu Qingqiang Wang Wenwen Wang Quan Bai Biliang Chen Xuebiao Yao Yong Chen
author_facet	Cheng Fang Wenhui Li Ruozhe Yin Donglie Zhu Xing Liu Huihui Wu Qingqiang Wang Wenwen Wang Quan Bai Biliang Chen Xuebiao Yao Yong Chen
author_sort	Cheng Fang
title	Potent antitumor activity of a glutamyltransferase-derived peptide via an activation of oncosis pathway
title_short	Potent antitumor activity of a glutamyltransferase-derived peptide via an activation of oncosis pathway
title_full	Potent antitumor activity of a glutamyltransferase-derived peptide via an activation of oncosis pathway
title_fullStr	Potent antitumor activity of a glutamyltransferase-derived peptide via an activation of oncosis pathway
title_full_unstemmed	Potent antitumor activity of a glutamyltransferase-derived peptide via an activation of oncosis pathway
title_sort	potent antitumor activity of a glutamyltransferase-derived peptide via an activation of oncosis pathway
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2ff30b6042fd422ea9764d949ca96111
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Potent antitumor activity of a glutamyltransferase-derived peptide via an activation of oncosis pathway

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