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Sodium cantharidate promotes autophagy in breast cancer cells by inhibiting the PI3K–Akt–mTOR signaling pathway

Sodium cantharidate (SCA) is a derivative of cantharidin obtained by its reaction with alkali. Studies have shown that it inhibits the occurrence and progression of several cancers. However, therapeutic effects of SCA on breast cancer are less well studied. This study aimed to clarify the effect of...

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Autores principales: Pang, Jin-Long, Xu, Lian-Song, Zhao, Qian, Niu, Wen-Wen, Rong, Xiang-Yu, Li, Shan-Shan, Li, Xian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9666387/
https://www.ncbi.nlm.nih.gov/pubmed/36408240
http://dx.doi.org/10.3389/fphar.2022.1000377
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author Pang, Jin-Long
Xu, Lian-Song
Zhao, Qian
Niu, Wen-Wen
Rong, Xiang-Yu
Li, Shan-Shan
Li, Xian
author_facet Pang, Jin-Long
Xu, Lian-Song
Zhao, Qian
Niu, Wen-Wen
Rong, Xiang-Yu
Li, Shan-Shan
Li, Xian
author_sort Pang, Jin-Long
collection PubMed
description Sodium cantharidate (SCA) is a derivative of cantharidin obtained by its reaction with alkali. Studies have shown that it inhibits the occurrence and progression of several cancers. However, therapeutic effects of SCA on breast cancer are less well studied. This study aimed to clarify the effect of SCA on breast cancer cells and its mechanism, and to provide a scientific basis for the clinical use of SCA for the treatment of breast cancer. The results of cell counting kit-8, colony formation assay, and 5-ethynyl-2′-deoxyuridine staining showed that SCA inhibited breast cancer cell proliferation. Wound-healing and transwell assays demonstrated that SCA inhibited the migration and invasion of breast cancer cells. Transmission electron microscopy revealed that SCA induced autophagy in breast cancer cells. RNA sequencing technology showed that SCA significantly regulated the phosphoinositide 3-kinase–Akt–mammalian target of rapamycin (PI3K–Akt–mTOR) pathway, which was further verified using western blotting. The inducing effect of SCA on breast cancer autophagy was reversed by the mTOR activator MHY1485. In addition, subcutaneous xenograft experiments confirmed that SCA significantly inhibited tumor growth in vivo. Hematoxylin-eosin, TdT-mediated dUTP nick-end labeling, and immunohistochemical staining indicated that SCA induced tumor cell autophagy and apoptosis in nude mice without causing organ damage. In summary, we found that SCA promoted breast cancer cell apoptosis by inhibiting the PI3K–Akt–mTOR pathway and inducing autophagy.
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spelling pubmed-96663872022-11-17 Sodium cantharidate promotes autophagy in breast cancer cells by inhibiting the PI3K–Akt–mTOR signaling pathway Pang, Jin-Long Xu, Lian-Song Zhao, Qian Niu, Wen-Wen Rong, Xiang-Yu Li, Shan-Shan Li, Xian Front Pharmacol Pharmacology Sodium cantharidate (SCA) is a derivative of cantharidin obtained by its reaction with alkali. Studies have shown that it inhibits the occurrence and progression of several cancers. However, therapeutic effects of SCA on breast cancer are less well studied. This study aimed to clarify the effect of SCA on breast cancer cells and its mechanism, and to provide a scientific basis for the clinical use of SCA for the treatment of breast cancer. The results of cell counting kit-8, colony formation assay, and 5-ethynyl-2′-deoxyuridine staining showed that SCA inhibited breast cancer cell proliferation. Wound-healing and transwell assays demonstrated that SCA inhibited the migration and invasion of breast cancer cells. Transmission electron microscopy revealed that SCA induced autophagy in breast cancer cells. RNA sequencing technology showed that SCA significantly regulated the phosphoinositide 3-kinase–Akt–mammalian target of rapamycin (PI3K–Akt–mTOR) pathway, which was further verified using western blotting. The inducing effect of SCA on breast cancer autophagy was reversed by the mTOR activator MHY1485. In addition, subcutaneous xenograft experiments confirmed that SCA significantly inhibited tumor growth in vivo. Hematoxylin-eosin, TdT-mediated dUTP nick-end labeling, and immunohistochemical staining indicated that SCA induced tumor cell autophagy and apoptosis in nude mice without causing organ damage. In summary, we found that SCA promoted breast cancer cell apoptosis by inhibiting the PI3K–Akt–mTOR pathway and inducing autophagy. Frontiers Media S.A. 2022-11-02 /pmc/articles/PMC9666387/ /pubmed/36408240 http://dx.doi.org/10.3389/fphar.2022.1000377 Text en Copyright © 2022 Pang, Xu, Zhao, Niu, Rong, Li and Li. https://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 Pharmacology
Pang, Jin-Long
Xu, Lian-Song
Zhao, Qian
Niu, Wen-Wen
Rong, Xiang-Yu
Li, Shan-Shan
Li, Xian
Sodium cantharidate promotes autophagy in breast cancer cells by inhibiting the PI3K–Akt–mTOR signaling pathway
title Sodium cantharidate promotes autophagy in breast cancer cells by inhibiting the PI3K–Akt–mTOR signaling pathway
title_full Sodium cantharidate promotes autophagy in breast cancer cells by inhibiting the PI3K–Akt–mTOR signaling pathway
title_fullStr Sodium cantharidate promotes autophagy in breast cancer cells by inhibiting the PI3K–Akt–mTOR signaling pathway
title_full_unstemmed Sodium cantharidate promotes autophagy in breast cancer cells by inhibiting the PI3K–Akt–mTOR signaling pathway
title_short Sodium cantharidate promotes autophagy in breast cancer cells by inhibiting the PI3K–Akt–mTOR signaling pathway
title_sort sodium cantharidate promotes autophagy in breast cancer cells by inhibiting the pi3k–akt–mtor signaling pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9666387/
https://www.ncbi.nlm.nih.gov/pubmed/36408240
http://dx.doi.org/10.3389/fphar.2022.1000377
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