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Cepharanthine as a Potential Novel Tumor-Regional Therapy in Treating Cutaneous Melanoma: Altering the Expression of Cathepsin B, Tumor Suppressor Genes and Autophagy-Related Proteins

The incidence of primary cutaneous melanoma continues to increase annually and is one of the most aggressive malignancies in humans and need to develop more novel non-surgical therapies. Autophagy and cathepsin B targeted therapy was reported to improve melanoma treatment. Cepharanthine (CEP), a nat...

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Autores principales: Liu, Yufang, Xie, Yang, Lin, Yao, Xu, Qingfang, Huang, Yunfen, Peng, Mengran, Lai, Wei, Zheng, Yue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736638/
https://www.ncbi.nlm.nih.gov/pubmed/33335896
http://dx.doi.org/10.3389/fbioe.2020.601969
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author Liu, Yufang
Xie, Yang
Lin, Yao
Xu, Qingfang
Huang, Yunfen
Peng, Mengran
Lai, Wei
Zheng, Yue
author_facet Liu, Yufang
Xie, Yang
Lin, Yao
Xu, Qingfang
Huang, Yunfen
Peng, Mengran
Lai, Wei
Zheng, Yue
author_sort Liu, Yufang
collection PubMed
description The incidence of primary cutaneous melanoma continues to increase annually and is one of the most aggressive malignancies in humans and need to develop more novel non-surgical therapies. Autophagy and cathepsin B targeted therapy was reported to improve melanoma treatment. Cepharanthine (CEP), a natural alkaloid extracted from the genus Cephalophyllum has been reported to have the function of inhibiting cancers. We found that CEP inhibited human primary cutaneous melanoma cells viability and proliferation in 24 h in vitro, and topical application or intra-tumoral injection of CEP decreased the growth of cutaneous melanoma in mice within 4 weeks. CEP preparations below 50% concentration did not induce skin irritation and allergy reaction on human skin in vivo. Primary cutaneous melanoma cells incubated with CEP, the expression of cathepsin B was decreased and the LC3-I and LC3-II expression changed in a dose-dependent manner, while p53, p21Cip1p, and p16Inka gene expression was up-regulated. We demonstrated the effects of CEP as a novel tumor-regional therapy for cutaneous melanoma and provided a preliminary research basis for future clinical treatment researches and the exploration of integrated treatments with systemic therapy, radiotherapy, and surgery for human primary cutaneous melanoma.
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spelling pubmed-77366382020-12-16 Cepharanthine as a Potential Novel Tumor-Regional Therapy in Treating Cutaneous Melanoma: Altering the Expression of Cathepsin B, Tumor Suppressor Genes and Autophagy-Related Proteins Liu, Yufang Xie, Yang Lin, Yao Xu, Qingfang Huang, Yunfen Peng, Mengran Lai, Wei Zheng, Yue Front Bioeng Biotechnol Bioengineering and Biotechnology The incidence of primary cutaneous melanoma continues to increase annually and is one of the most aggressive malignancies in humans and need to develop more novel non-surgical therapies. Autophagy and cathepsin B targeted therapy was reported to improve melanoma treatment. Cepharanthine (CEP), a natural alkaloid extracted from the genus Cephalophyllum has been reported to have the function of inhibiting cancers. We found that CEP inhibited human primary cutaneous melanoma cells viability and proliferation in 24 h in vitro, and topical application or intra-tumoral injection of CEP decreased the growth of cutaneous melanoma in mice within 4 weeks. CEP preparations below 50% concentration did not induce skin irritation and allergy reaction on human skin in vivo. Primary cutaneous melanoma cells incubated with CEP, the expression of cathepsin B was decreased and the LC3-I and LC3-II expression changed in a dose-dependent manner, while p53, p21Cip1p, and p16Inka gene expression was up-regulated. We demonstrated the effects of CEP as a novel tumor-regional therapy for cutaneous melanoma and provided a preliminary research basis for future clinical treatment researches and the exploration of integrated treatments with systemic therapy, radiotherapy, and surgery for human primary cutaneous melanoma. Frontiers Media S.A. 2020-12-01 /pmc/articles/PMC7736638/ /pubmed/33335896 http://dx.doi.org/10.3389/fbioe.2020.601969 Text en Copyright © 2020 Liu, Xie, Lin, Xu, Huang, Peng, Lai and Zheng. http://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 Bioengineering and Biotechnology
Liu, Yufang
Xie, Yang
Lin, Yao
Xu, Qingfang
Huang, Yunfen
Peng, Mengran
Lai, Wei
Zheng, Yue
Cepharanthine as a Potential Novel Tumor-Regional Therapy in Treating Cutaneous Melanoma: Altering the Expression of Cathepsin B, Tumor Suppressor Genes and Autophagy-Related Proteins
title Cepharanthine as a Potential Novel Tumor-Regional Therapy in Treating Cutaneous Melanoma: Altering the Expression of Cathepsin B, Tumor Suppressor Genes and Autophagy-Related Proteins
title_full Cepharanthine as a Potential Novel Tumor-Regional Therapy in Treating Cutaneous Melanoma: Altering the Expression of Cathepsin B, Tumor Suppressor Genes and Autophagy-Related Proteins
title_fullStr Cepharanthine as a Potential Novel Tumor-Regional Therapy in Treating Cutaneous Melanoma: Altering the Expression of Cathepsin B, Tumor Suppressor Genes and Autophagy-Related Proteins
title_full_unstemmed Cepharanthine as a Potential Novel Tumor-Regional Therapy in Treating Cutaneous Melanoma: Altering the Expression of Cathepsin B, Tumor Suppressor Genes and Autophagy-Related Proteins
title_short Cepharanthine as a Potential Novel Tumor-Regional Therapy in Treating Cutaneous Melanoma: Altering the Expression of Cathepsin B, Tumor Suppressor Genes and Autophagy-Related Proteins
title_sort cepharanthine as a potential novel tumor-regional therapy in treating cutaneous melanoma: altering the expression of cathepsin b, tumor suppressor genes and autophagy-related proteins
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736638/
https://www.ncbi.nlm.nih.gov/pubmed/33335896
http://dx.doi.org/10.3389/fbioe.2020.601969
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