Cargando…

Tubulin‐binding peptide RR‐171 derived from human umbilical cord serum displays antitumor activity against hepatocellular carcinoma via inducing apoptosis and activating the NF‐kappa B pathway

OBJECTIVES: Hepatocellular carcinoma (HCC) still presents a high incidence of malignant tumours with poor prognosis. There is an urgent need for new therapeutic agents with high specificity, low toxicity and favourable solubility for the clinical treatment of HCC. MATERIALS AND METHODS: The bioactiv...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Donglie, Fang, Cheng, Yang, Zelong, Ren, Yanjie, Yang, Fengrui, Zheng, Shi, Jiang, Mingzuo, Miao, Xiangxia, Liu, Duoduo, Chen, Biliang, Yao, Xuebiao, Chen, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136518/
https://www.ncbi.nlm.nih.gov/pubmed/35504605
http://dx.doi.org/10.1111/cpr.13241
_version_ 1784714200275222528
author Zhu, Donglie
Fang, Cheng
Yang, Zelong
Ren, Yanjie
Yang, Fengrui
Zheng, Shi
Jiang, Mingzuo
Miao, Xiangxia
Liu, Duoduo
Chen, Biliang
Yao, Xuebiao
Chen, Yong
author_facet Zhu, Donglie
Fang, Cheng
Yang, Zelong
Ren, Yanjie
Yang, Fengrui
Zheng, Shi
Jiang, Mingzuo
Miao, Xiangxia
Liu, Duoduo
Chen, Biliang
Yao, Xuebiao
Chen, Yong
author_sort Zhu, Donglie
collection PubMed
description OBJECTIVES: Hepatocellular carcinoma (HCC) still presents a high incidence of malignant tumours with poor prognosis. There is an urgent need for new therapeutic agents with high specificity, low toxicity and favourable solubility for the clinical treatment of HCC. MATERIALS AND METHODS: The bioactivity of human umbilical cord serum was investigated by proteomics biotechnology and a primitive peptide with certain biological activity was identified. The antitumour effect of RR‐171 was detected by cell viability assay in vitro, and determined by subcutaneous xenograft models assay and miniPDX assay in vivo. Pull‐down experiments were conducted to identify the potential targeting proteins of RR‐171. Immunofluorescence assay and tubulin polymerization assay were conducted to explore the relationship between RR‐171 and α‐tubulin. Fluorescence imaging in xenograft models was used to explore the biodistribution of RR‐171 in vivo. A phosphospecific protein microarray was performed to uncover the underlying signalling pathway by which RR‐171 induces tumour cell death. RESULTS: The results indicated that RR‐171 could be effective in the treatment of HCC in vivo and in vitro. RR‐171 could aggregate significantly in solid tumours and had no obvious systemic toxicity in vivo. RR‐171 could interact with α‐tubulin and activate the NF‐Kappa B pathway in HCC cells. CONCLUSIONS: Taken together, RR‐171 exhibited significant antitumour activity against HCC in vivo and in vitro and could potentially be used in the clinical application of HCC.
format Online
Article
Text
id pubmed-9136518
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-91365182022-06-04 Tubulin‐binding peptide RR‐171 derived from human umbilical cord serum displays antitumor activity against hepatocellular carcinoma via inducing apoptosis and activating the NF‐kappa B pathway Zhu, Donglie Fang, Cheng Yang, Zelong Ren, Yanjie Yang, Fengrui Zheng, Shi Jiang, Mingzuo Miao, Xiangxia Liu, Duoduo Chen, Biliang Yao, Xuebiao Chen, Yong Cell Prolif Original Articles OBJECTIVES: Hepatocellular carcinoma (HCC) still presents a high incidence of malignant tumours with poor prognosis. There is an urgent need for new therapeutic agents with high specificity, low toxicity and favourable solubility for the clinical treatment of HCC. MATERIALS AND METHODS: The bioactivity of human umbilical cord serum was investigated by proteomics biotechnology and a primitive peptide with certain biological activity was identified. The antitumour effect of RR‐171 was detected by cell viability assay in vitro, and determined by subcutaneous xenograft models assay and miniPDX assay in vivo. Pull‐down experiments were conducted to identify the potential targeting proteins of RR‐171. Immunofluorescence assay and tubulin polymerization assay were conducted to explore the relationship between RR‐171 and α‐tubulin. Fluorescence imaging in xenograft models was used to explore the biodistribution of RR‐171 in vivo. A phosphospecific protein microarray was performed to uncover the underlying signalling pathway by which RR‐171 induces tumour cell death. RESULTS: The results indicated that RR‐171 could be effective in the treatment of HCC in vivo and in vitro. RR‐171 could aggregate significantly in solid tumours and had no obvious systemic toxicity in vivo. RR‐171 could interact with α‐tubulin and activate the NF‐Kappa B pathway in HCC cells. CONCLUSIONS: Taken together, RR‐171 exhibited significant antitumour activity against HCC in vivo and in vitro and could potentially be used in the clinical application of HCC. John Wiley and Sons Inc. 2022-05-03 /pmc/articles/PMC9136518/ /pubmed/35504605 http://dx.doi.org/10.1111/cpr.13241 Text en © 2022 The Authors. Cell Proliferation published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Zhu, Donglie
Fang, Cheng
Yang, Zelong
Ren, Yanjie
Yang, Fengrui
Zheng, Shi
Jiang, Mingzuo
Miao, Xiangxia
Liu, Duoduo
Chen, Biliang
Yao, Xuebiao
Chen, Yong
Tubulin‐binding peptide RR‐171 derived from human umbilical cord serum displays antitumor activity against hepatocellular carcinoma via inducing apoptosis and activating the NF‐kappa B pathway
title Tubulin‐binding peptide RR‐171 derived from human umbilical cord serum displays antitumor activity against hepatocellular carcinoma via inducing apoptosis and activating the NF‐kappa B pathway
title_full Tubulin‐binding peptide RR‐171 derived from human umbilical cord serum displays antitumor activity against hepatocellular carcinoma via inducing apoptosis and activating the NF‐kappa B pathway
title_fullStr Tubulin‐binding peptide RR‐171 derived from human umbilical cord serum displays antitumor activity against hepatocellular carcinoma via inducing apoptosis and activating the NF‐kappa B pathway
title_full_unstemmed Tubulin‐binding peptide RR‐171 derived from human umbilical cord serum displays antitumor activity against hepatocellular carcinoma via inducing apoptosis and activating the NF‐kappa B pathway
title_short Tubulin‐binding peptide RR‐171 derived from human umbilical cord serum displays antitumor activity against hepatocellular carcinoma via inducing apoptosis and activating the NF‐kappa B pathway
title_sort tubulin‐binding peptide rr‐171 derived from human umbilical cord serum displays antitumor activity against hepatocellular carcinoma via inducing apoptosis and activating the nf‐kappa b pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136518/
https://www.ncbi.nlm.nih.gov/pubmed/35504605
http://dx.doi.org/10.1111/cpr.13241
work_keys_str_mv AT zhudonglie tubulinbindingpeptiderr171derivedfromhumanumbilicalcordserumdisplaysantitumoractivityagainsthepatocellularcarcinomaviainducingapoptosisandactivatingthenfkappabpathway
AT fangcheng tubulinbindingpeptiderr171derivedfromhumanumbilicalcordserumdisplaysantitumoractivityagainsthepatocellularcarcinomaviainducingapoptosisandactivatingthenfkappabpathway
AT yangzelong tubulinbindingpeptiderr171derivedfromhumanumbilicalcordserumdisplaysantitumoractivityagainsthepatocellularcarcinomaviainducingapoptosisandactivatingthenfkappabpathway
AT renyanjie tubulinbindingpeptiderr171derivedfromhumanumbilicalcordserumdisplaysantitumoractivityagainsthepatocellularcarcinomaviainducingapoptosisandactivatingthenfkappabpathway
AT yangfengrui tubulinbindingpeptiderr171derivedfromhumanumbilicalcordserumdisplaysantitumoractivityagainsthepatocellularcarcinomaviainducingapoptosisandactivatingthenfkappabpathway
AT zhengshi tubulinbindingpeptiderr171derivedfromhumanumbilicalcordserumdisplaysantitumoractivityagainsthepatocellularcarcinomaviainducingapoptosisandactivatingthenfkappabpathway
AT jiangmingzuo tubulinbindingpeptiderr171derivedfromhumanumbilicalcordserumdisplaysantitumoractivityagainsthepatocellularcarcinomaviainducingapoptosisandactivatingthenfkappabpathway
AT miaoxiangxia tubulinbindingpeptiderr171derivedfromhumanumbilicalcordserumdisplaysantitumoractivityagainsthepatocellularcarcinomaviainducingapoptosisandactivatingthenfkappabpathway
AT liuduoduo tubulinbindingpeptiderr171derivedfromhumanumbilicalcordserumdisplaysantitumoractivityagainsthepatocellularcarcinomaviainducingapoptosisandactivatingthenfkappabpathway
AT chenbiliang tubulinbindingpeptiderr171derivedfromhumanumbilicalcordserumdisplaysantitumoractivityagainsthepatocellularcarcinomaviainducingapoptosisandactivatingthenfkappabpathway
AT yaoxuebiao tubulinbindingpeptiderr171derivedfromhumanumbilicalcordserumdisplaysantitumoractivityagainsthepatocellularcarcinomaviainducingapoptosisandactivatingthenfkappabpathway
AT chenyong tubulinbindingpeptiderr171derivedfromhumanumbilicalcordserumdisplaysantitumoractivityagainsthepatocellularcarcinomaviainducingapoptosisandactivatingthenfkappabpathway