<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Development of chemoresistance remains a significant limitation for the treatment of cancer and contributes to recurrence of the disease. Both intrinsic and acquired mechanisms of chemoresistance are characteristics of cancer stem cells (CSCs) or stem-like cells (SLCs). The aim of the study was to assess the stem-like properties in the breast cancer cell line MDA-MB-231 during and after pulsed treatment with doxorubicin (DOX) in comparison to the untreated controls.The experimental cultures were exposed to therapeutic concentration of DOX for 48 hours (treatment cultures), and subcultured to post-treatment cultures 24 hours after the removal of DOX. Stem-like properties of the cellular populations in the treatment and post--treatment cultures were assessed by the expression of the stem-cell marker genes (<italic>CD24, CD44, ITGA6, ITGB1, POU5F1, NANOG, ALDH1A1</italic>), colony-formation efficiency, growth rates, and sensitivity to DOX, 5-fluorouracil (5FU), cisplatin (CIS), and vinblastine (VBL). Exposure to DOX induced formation of giant polyploid cells that persisted in the post-treatment culture. The recovery period was characterised by a decrease in the proliferation rate, viability, and cellular adherence. The post-treatment cultures displayed decreased sensitivity to DOX and increased sensitivities to 5FU, CIS, and VBL. Cells treated with DOX displayed increased expression levels of <italic>CD24, CD44,</italic> and <italic>ALDH1A</italic>, while their expression levels at least partially normalised in the post-treatment culture. The post-treatment cultures demonstrated significantly increased colony-formation ability. During treatment with sub-lethal levels of doxorubicin and during the acute recovery period, the survival mechanisms in the breast cancer cell line MDA-MB-231 may be mediated by formation of the cellular population with stem-like properties.</p></abstract>

Development of chemoresistance remains a significant limitation for the treatment of cancer and contributes to recurrence of the disease. Both intrinsic and acquired mechanisms of chemoresistance are characteristics of cancer stem cells (CSCs) or stem-like cells (SLCs). The aim of the study was to assess the stem-like properties in the breast cancer cell line MDA-MB-231 during and after pulsed treatment with doxorubicin (DOX) in comparison to the untreated controls.The experimental cultures were exposed to therapeutic concentration of DOX for 48 hours (treatment cultures), and subcultured to post-treatment cultures 24 hours after the removal of DOX. Stem-like properties of the cellular populations in the treatment and post--treatment cultures were assessed by the expression of the stem-cell marker genes (CD24, CD44, ITGA6, ITGB1, POU5F1, NANOG, ALDH1A1), colony-formation efficiency, growth rates, and sensitivity to DOX, 5-fluorouracil (5FU), cisplatin (CIS), and vinblastine (VBL). Exposure to DOX induced formation of giant polyploid cells that persisted in the post-treatment culture. The recovery period was characterised by a decrease in the proliferation rate, viability, and cellular adherence. The post-treatment cultures displayed decreased sensitivity to DOX and increased sensitivities to 5FU, CIS, and VBL. Cells treated with DOX displayed increased expression levels of CD24, CD44, and ALDH1A, while their expression levels at least partially normalised in the post-treatment culture. The post-treatment cultures demonstrated significantly increased colony-formation ability. During treatment with sub-lethal levels of doxorubicin and during the acute recovery period, the survival mechanisms in the breast cancer cell line MDA-MB-231 may be mediated by formation of the cellular population with stem-like properties.

Alterations of The Stem-Like Properties in The Breast Cancer Cell Line MDA-MB-231 Induced by Single Pulsed Doxorubicin Treatment

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Development of chemoresistance remains a significant limitation for the treatment of cancer and contributes to recurrence of the disease. Both intrinsic and...

Alterations of The Stem-Like Properties in The Breast Cancer Cell Line MDA-MB-231 Induced by Single Pulsed Doxorubicin Treatment

Published Online: Apr 07, 2019

Page range: 89 - 99

Received: Nov 07, 2018

Accepted: Feb 06, 2019

DOI: https://doi.org/10.2478/prolas-2019-0015

Keywords
chemotherapy resistance, cancer stem-like cells (cSCLs), stem-cell marker genes

© 2019 Valdis Pirsko et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Alterations of The Stem-Like Properties in The Breast Cancer Cell Line MDA-MB-231 Induced by Single Pulsed Doxorubicin Treatment

Published Online: Apr 07, 2019

Page range: 89 - 99

Received: Nov 07, 2018

Accepted: Feb 06, 2019

DOI: https://doi.org/10.2478/prolas-2019-0015

Keywordschemotherapy resistance, cancer stem-like cells (cSCLs), stem-cell marker genes

© 2019 Valdis Pirsko et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Keywords
chemotherapy resistance, cancer stem-like cells (cSCLs), stem-cell marker genes