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Novel strategies to target chemoresistant triple-negative breast cancer

Previous studies from our group and others have shown that current drug treatment(s) strategies eliminate bulk of tumor cells (non-CSCs) but it had a minimal effect on cancer stem cells (CSCs) leading to resistance and tumor recurrence. We studied the effects of CFM-4.16 (CARP-1 functional mimetic)...

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Autores principales: Venkatesh, Jaganathan, Rishi, Arun K., Reddy, Kaladhar B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805540/
https://www.ncbi.nlm.nih.gov/pubmed/33488948
http://dx.doi.org/10.18632/genesandcancer.204
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author Venkatesh, Jaganathan
Rishi, Arun K.
Reddy, Kaladhar B.
author_facet Venkatesh, Jaganathan
Rishi, Arun K.
Reddy, Kaladhar B.
author_sort Venkatesh, Jaganathan
collection PubMed
description Previous studies from our group and others have shown that current drug treatment(s) strategies eliminate bulk of tumor cells (non-CSCs) but it had a minimal effect on cancer stem cells (CSCs) leading to resistance and tumor recurrence. We studied the effects of CFM-4.16 (CARP-1 functional mimetic) and/or cisplatin on four Triple-negative breast cancer (TNBC) MDA-MB-468, MDA-MB-231, CRL-2335 and BR-1126, two cisplatin resistant CisR/MDA-231 and CisR/MDA-468 and cancer stem cells (CSCs) from resistant cell lines. TNBC cells treated with CFM-4.16 plus cisplatin inhibited the expression of FZD8, LRP6 and c-Myc and significantly enhanced cell death in all the cell lines by ~70%-80% compared with the control(s). When Cisplatin resistant CisR/MDA-231 and CisR/MDA-468 were treated with CFM-4.16 plus cisplatin, they also showed a reduction in FZD8 and LRP6 and increased apoptosis compared to control group. Similarly, CFM-4.16 plus cisplatin treatment reduced mammospheres formation abilities of CSCs by 80-90% compared to control group, increased PARP cleavage and apoptosis. Data shows CFM-4.16 plus cisplatin treatment significantly increased apoptosis/cell death in parental, cisplatin resistant and CSCs. Taken together the data suggests that FZD8-mediated Wnt-signaling plays a major role in mediating CSCs growth and resistance to chemotherapy and its inhibition enhances the chemotherapeutic response in TNBC.
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spelling pubmed-78055402021-01-21 Novel strategies to target chemoresistant triple-negative breast cancer Venkatesh, Jaganathan Rishi, Arun K. Reddy, Kaladhar B. Genes Cancer Research Paper Previous studies from our group and others have shown that current drug treatment(s) strategies eliminate bulk of tumor cells (non-CSCs) but it had a minimal effect on cancer stem cells (CSCs) leading to resistance and tumor recurrence. We studied the effects of CFM-4.16 (CARP-1 functional mimetic) and/or cisplatin on four Triple-negative breast cancer (TNBC) MDA-MB-468, MDA-MB-231, CRL-2335 and BR-1126, two cisplatin resistant CisR/MDA-231 and CisR/MDA-468 and cancer stem cells (CSCs) from resistant cell lines. TNBC cells treated with CFM-4.16 plus cisplatin inhibited the expression of FZD8, LRP6 and c-Myc and significantly enhanced cell death in all the cell lines by ~70%-80% compared with the control(s). When Cisplatin resistant CisR/MDA-231 and CisR/MDA-468 were treated with CFM-4.16 plus cisplatin, they also showed a reduction in FZD8 and LRP6 and increased apoptosis compared to control group. Similarly, CFM-4.16 plus cisplatin treatment reduced mammospheres formation abilities of CSCs by 80-90% compared to control group, increased PARP cleavage and apoptosis. Data shows CFM-4.16 plus cisplatin treatment significantly increased apoptosis/cell death in parental, cisplatin resistant and CSCs. Taken together the data suggests that FZD8-mediated Wnt-signaling plays a major role in mediating CSCs growth and resistance to chemotherapy and its inhibition enhances the chemotherapeutic response in TNBC. Impact Journals LLC 2020-07-22 /pmc/articles/PMC7805540/ /pubmed/33488948 http://dx.doi.org/10.18632/genesandcancer.204 Text en Copyright: © 2020 Venkatesh et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Venkatesh, Jaganathan
Rishi, Arun K.
Reddy, Kaladhar B.
Novel strategies to target chemoresistant triple-negative breast cancer
title Novel strategies to target chemoresistant triple-negative breast cancer
title_full Novel strategies to target chemoresistant triple-negative breast cancer
title_fullStr Novel strategies to target chemoresistant triple-negative breast cancer
title_full_unstemmed Novel strategies to target chemoresistant triple-negative breast cancer
title_short Novel strategies to target chemoresistant triple-negative breast cancer
title_sort novel strategies to target chemoresistant triple-negative breast cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805540/
https://www.ncbi.nlm.nih.gov/pubmed/33488948
http://dx.doi.org/10.18632/genesandcancer.204
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