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Alkaloid Derivative (Z)-3β-Ethylamino-Pregn-17(20)-en Inhibits Triple-Negative Breast Cancer Metastasis and Angiogenesis by Targeting HSP90α

Metastasis is an important cause of cancer-related death. Previous studies in our laboratory found that pregnane alkaloids from Pachysandra terminalis had antimetastatic activity against breast cancer cells. In the current study, we demonstrated that treatment with one of the alkaloid derivatives, (...

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Autores principales: Liu, Xin-Yao, Wang, Yu-Miao, Zhang, Xiang-Yu, Jia, Mei-Qi, Duan, Hong-Quan, Qin, Nan, Chen, Ying, Yu, Yang, Duan, Xiao-Chuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9611734/
https://www.ncbi.nlm.nih.gov/pubmed/36296726
http://dx.doi.org/10.3390/molecules27207132
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author Liu, Xin-Yao
Wang, Yu-Miao
Zhang, Xiang-Yu
Jia, Mei-Qi
Duan, Hong-Quan
Qin, Nan
Chen, Ying
Yu, Yang
Duan, Xiao-Chuan
author_facet Liu, Xin-Yao
Wang, Yu-Miao
Zhang, Xiang-Yu
Jia, Mei-Qi
Duan, Hong-Quan
Qin, Nan
Chen, Ying
Yu, Yang
Duan, Xiao-Chuan
author_sort Liu, Xin-Yao
collection PubMed
description Metastasis is an important cause of cancer-related death. Previous studies in our laboratory found that pregnane alkaloids from Pachysandra terminalis had antimetastatic activity against breast cancer cells. In the current study, we demonstrated that treatment with one of the alkaloid derivatives, (Z)-3β-ethylamino-pregn-17(20)-en (1), led to the downregulation of the HIF-1α/VEGF/VEGFR2 pathway, suppressed the phosphorylation of downstream molecules Akt, mTOR, FAK, and inhibited breast cancer metastasis and angiogenesis both in vitro and in vivo. Furthermore, the antimetastasis and antiangiogenesis effects of 1 treatment (40 mg/kg) were more effective than that of Sorafenib (50 mg/kg). Surface plasmon resonance (SPR) analysis was performed and the result suggested that HSP90α was a direct target of 1. Taken together, our results suggested that compound 1 might represent a candidate antitumor agent for metastatic breast cancer.
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spelling pubmed-96117342022-10-28 Alkaloid Derivative (Z)-3β-Ethylamino-Pregn-17(20)-en Inhibits Triple-Negative Breast Cancer Metastasis and Angiogenesis by Targeting HSP90α Liu, Xin-Yao Wang, Yu-Miao Zhang, Xiang-Yu Jia, Mei-Qi Duan, Hong-Quan Qin, Nan Chen, Ying Yu, Yang Duan, Xiao-Chuan Molecules Article Metastasis is an important cause of cancer-related death. Previous studies in our laboratory found that pregnane alkaloids from Pachysandra terminalis had antimetastatic activity against breast cancer cells. In the current study, we demonstrated that treatment with one of the alkaloid derivatives, (Z)-3β-ethylamino-pregn-17(20)-en (1), led to the downregulation of the HIF-1α/VEGF/VEGFR2 pathway, suppressed the phosphorylation of downstream molecules Akt, mTOR, FAK, and inhibited breast cancer metastasis and angiogenesis both in vitro and in vivo. Furthermore, the antimetastasis and antiangiogenesis effects of 1 treatment (40 mg/kg) were more effective than that of Sorafenib (50 mg/kg). Surface plasmon resonance (SPR) analysis was performed and the result suggested that HSP90α was a direct target of 1. Taken together, our results suggested that compound 1 might represent a candidate antitumor agent for metastatic breast cancer. MDPI 2022-10-21 /pmc/articles/PMC9611734/ /pubmed/36296726 http://dx.doi.org/10.3390/molecules27207132 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Xin-Yao
Wang, Yu-Miao
Zhang, Xiang-Yu
Jia, Mei-Qi
Duan, Hong-Quan
Qin, Nan
Chen, Ying
Yu, Yang
Duan, Xiao-Chuan
Alkaloid Derivative (Z)-3β-Ethylamino-Pregn-17(20)-en Inhibits Triple-Negative Breast Cancer Metastasis and Angiogenesis by Targeting HSP90α
title Alkaloid Derivative (Z)-3β-Ethylamino-Pregn-17(20)-en Inhibits Triple-Negative Breast Cancer Metastasis and Angiogenesis by Targeting HSP90α
title_full Alkaloid Derivative (Z)-3β-Ethylamino-Pregn-17(20)-en Inhibits Triple-Negative Breast Cancer Metastasis and Angiogenesis by Targeting HSP90α
title_fullStr Alkaloid Derivative (Z)-3β-Ethylamino-Pregn-17(20)-en Inhibits Triple-Negative Breast Cancer Metastasis and Angiogenesis by Targeting HSP90α
title_full_unstemmed Alkaloid Derivative (Z)-3β-Ethylamino-Pregn-17(20)-en Inhibits Triple-Negative Breast Cancer Metastasis and Angiogenesis by Targeting HSP90α
title_short Alkaloid Derivative (Z)-3β-Ethylamino-Pregn-17(20)-en Inhibits Triple-Negative Breast Cancer Metastasis and Angiogenesis by Targeting HSP90α
title_sort alkaloid derivative (z)-3β-ethylamino-pregn-17(20)-en inhibits triple-negative breast cancer metastasis and angiogenesis by targeting hsp90α
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9611734/
https://www.ncbi.nlm.nih.gov/pubmed/36296726
http://dx.doi.org/10.3390/molecules27207132
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