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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, (...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9611734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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