M. du Plessis, C. Fourie, Heloise le Roux, A. Engelbrecht
{"title":"Sanguinarine highly sensitises breast cancer cells to doxorubicin-induced apoptosis","authors":"M. du Plessis, C. Fourie, Heloise le Roux, A. Engelbrecht","doi":"10.17159/sajs.2024/14917","DOIUrl":null,"url":null,"abstract":"Breast cancer is the most commonly diagnosed cancer and the second most common cause of cancer death in women. The anthracycline, doxorubicin, is a well-known and highly effective treatment for breast cancer patients; however, many patients present with resistance to chemotherapeutic drugs, which ultimately results in treatment failure and contributes to high mortality rates. It is well established that the mitogen-activated protein kinase phosphatase 1 (MKP-1) mediates the response to chemotherapy, where upregulated MKP-1 is associated with chemoresistance. We investigated whether MKP-1 inhibition or silencing can sensitise triple-negative MDA-MB-231 breast cancer cells to doxorubicin therapy. We found that MKP-1 inhibition and silencing sensitises breast cancer cells to doxorubicin-induced apoptosis. Additionally, the inhibition of MKP-1 in combination with doxorubicin treatment promotes autophagy induction, while doxorubicin and not MKP-1 modulation increased lysosomal acidic compartments. As such, this study demonstrated that MKP-1 inhibition has a potential therapeutic benefit for breast cancer patients by increasing the efficacy of conventional chemotherapy. Therefore, MKP-1 inhibition should be developed as a clinically relevant adjuvant therapy, which could provide a novel avenue for therapeutic intervention in combination with chemotherapy in breast cancer patients.","PeriodicalId":21928,"journal":{"name":"South African Journal of Science","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"South African Journal of Science","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.17159/sajs.2024/14917","RegionNum":4,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Breast cancer is the most commonly diagnosed cancer and the second most common cause of cancer death in women. The anthracycline, doxorubicin, is a well-known and highly effective treatment for breast cancer patients; however, many patients present with resistance to chemotherapeutic drugs, which ultimately results in treatment failure and contributes to high mortality rates. It is well established that the mitogen-activated protein kinase phosphatase 1 (MKP-1) mediates the response to chemotherapy, where upregulated MKP-1 is associated with chemoresistance. We investigated whether MKP-1 inhibition or silencing can sensitise triple-negative MDA-MB-231 breast cancer cells to doxorubicin therapy. We found that MKP-1 inhibition and silencing sensitises breast cancer cells to doxorubicin-induced apoptosis. Additionally, the inhibition of MKP-1 in combination with doxorubicin treatment promotes autophagy induction, while doxorubicin and not MKP-1 modulation increased lysosomal acidic compartments. As such, this study demonstrated that MKP-1 inhibition has a potential therapeutic benefit for breast cancer patients by increasing the efficacy of conventional chemotherapy. Therefore, MKP-1 inhibition should be developed as a clinically relevant adjuvant therapy, which could provide a novel avenue for therapeutic intervention in combination with chemotherapy in breast cancer patients.
期刊介绍:
The South African Journal of Science is a multidisciplinary journal published bimonthly by the Academy of Science of South Africa. Our mandate is to publish original research with an interdisciplinary or regional focus, which will interest readers from more than one discipline, and to provide a forum for discussion of news and developments in research and higher education. Authors are requested to write their papers and reports in a manner and style that is intelligible to specialists and non-specialists alike. Research contributions, which are peer reviewed, are of three kinds: Review Articles, Research Articles and Research Letters.