Amino acid starvation sensitizes resistant breast cancer to doxorubicin-induced cell death

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dc.contributor.authorThomas, Marken_ZA
dc.contributor.authorDavis, Tanja Andreaen_ZA
dc.contributor.authorNell, Theoen_ZA
dc.contributor.authorSishi, Balindiwe J. N. (Jennifer Nonkosazana)en_ZA
dc.contributor.authorEngelbrecht, Anna-Marten_ZA
dc.date.accessioned2020-10-19T11:13:29Z
dc.date.available2020-10-19T11:13:29Z
dc.date.issued2020
dc.descriptionCITATION: Thomas, M., et al. 2020. Amino acid starvation sensitizes resistant breast cancer to doxorubicin-induced cell death. Frontiers in Cell and Developmental Biology, 8:565915, doi:10.3389/fcell.2020.565915.
dc.descriptionThe original publication is available at https://www.frontiersin.org/articles/10.3389/fcell.2020.565915/full
dc.descriptionPublication of this article was funded by the Stellenbosch University Open Access Fund
dc.description.abstractMany clinical trials are beginning to assess the effectiveness of compounds known to regulate autophagy in patients receiving anti-cancer chemotherapy. However, autophagy inhibition, through exogenous inhibitors, or activation, through starvation, has revealed conflicting roles in cancer management and chemotherapeutic outcome. This study aimed to assess the effect of amino acid starvation on doxorubicin-treated breast cancer cells by assessing the roles of autophagy and apoptosis. An in vitro breast cancer model consisting of the normal breast epithelial MCF12A and the metastatic breast cancer MDAMB231 cells was used. Apoptotic and autophagic parameters were assessed following doxorubicin treatments, alone or in combination with bafilomycin, ATG5 siRNA or amino acid starvation. Inhibition of autophagy, through ATG5 siRNA or bafilomycin treatment, increased caspase activity and intracellular doxorubicin concentrations in MCF12A and MDAMB231 cells during doxorubicin treatment. While amino acid starvation increased autophagic activity and decreased caspase activity and intracellular doxorubicin concentrations in MCF12A cells, no changes in autophagic parameters or caspase activity were observed in MDAMB231 cells. Our in vivo data showed that 24 h protein starvation during high dose doxorubicin treatment resulted in increased survival of tumor-bearing GFP-LC3 mice. Results from this study suggest that short term starvation during doxorubicin chemotherapy may be a realistic avenue for adjuvant therapy, especially with regards to the protection of non-cancerous cells. More research is however, needed to fully understand the regulation of autophagic flux during starvation.en_ZA
dc.description.urihttps://www.frontiersin.org/articles/10.3389/fcell.2020.565915/full
dc.description.versionPublisher's version
dc.format.extent18 pages : illustrations
dc.identifier.citationThomas, M., et al. 2020. Amino acid starvation sensitizes resistant breast cancer to doxorubicin-induced cell death. Frontiers in Cell and Developmental Biology, 8:565915, doi:10.3389/fcell.2020.565915
dc.identifier.issn1663-9812 (online)
dc.identifier.otherdoi:10.3389/fcell.2020.565915
dc.identifier.urihttp://hdl.handle.net/10019.1/108898
dc.language.isoen_ZAen_ZA
dc.publisherFrontiers Media
dc.rights.holderAuthors retain copyright
dc.subjectAmino acids in nutritionen_ZA
dc.subjectDrug resistance in cancer cellsen_ZA
dc.subjectBreast canceren_ZA
dc.subjectBreast -- Cancer -- Chemotherapyen_ZA
dc.subjectBreast -- Cancer -- Researchen_ZA
dc.subjectDoxorubicin -- Side effectsen_ZA
dc.subjectDoxorubicin -- Cancer -- Chemotherapyen_ZA
dc.titleAmino acid starvation sensitizes resistant breast cancer to doxorubicin-induced cell deathen_ZA
dc.typeArticleen_ZA
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