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Updated: Aug 25, 2025
Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
Targeting Triple Negative Breast Cancer Stem Cells by Heat Shock Protein 70 Inhibitors
Chia-Hung Tsai1, Jing-Ru Weng2,3, Hsiang-Wen Lin4,5
1Department of Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427213, Taiwan.
Abstract:
Triple negative breast cancer (TNBC) is considered the most aggressive breast cancer with high relapse rates and poor prognosis. Although great advances in the development of cancer therapy have been witnessed over the past decade, the treatment options for TNBC remain limited. In this study, we investigated the effect and potential underlying mechanism of the Hsp70 inhibitors, compound 1 and compound 6, on breast cancer stem cells (BCSCs) in TNBC cells. Our results showed that compound 1 and 6 exhibited potent tumor suppressive effects on cell viability and proliferation, and effectively inhibited BCSC expansion in TNBC cells. Reminiscent with the effect of Hsp70 inhibitors, Hsp70 knockdown effectively suppressed mammosphere formation and the expressions of BCSCs surface markers. Mechanistically, evidence showed that the Hsp70 inhibitors inhibited BCSCs by down-regulating β-catenin in TNBC cells. Moreover, we used the Hsp70 inhibitors treated TNBC cells and a stable Hsp70 knockdown clone of MDA-MB-231 cells to demonstrate the in vivo efficacy of Hsp70 inhibition in suppressing tumorigenesis and xenograft tumor growth. Together, these findings suggest the potential role of Hsp70 as a target for TNBC therapy and foster new therapeutic strategies to eliminate BCSCs by targeting Hsp70.
Insights
Hsp70 inhibitors show promise in treating triple negative breast cancer (TNBC). These compounds suppress cancer stem cells and tumor growth by targeting the beta-catenin pathway, offering new therapeutic strategies for TNBC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Triple negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and high recurrence rates.
- Breast cancer stem cells (BCSCs) are implicated in TNBC's resistance to therapy and relapse.
- Heat shock protein 70 (Hsp70) is a potential therapeutic target in various cancers.
Purpose of the Study:
- To investigate the efficacy of Hsp70 inhibitors (compound 1 and compound 6) against BCSCs in TNBC.
- To elucidate the underlying molecular mechanisms of Hsp70 inhibition in TNBC.
- To evaluate the in vivo therapeutic potential of targeting Hsp70 in TNBC models.
Main Methods:
- Treatment of TNBC cells with Hsp70 inhibitors (compound 1, compound 6) and Hsp70 knockdown.
- Assessment of cell viability, proliferation, and BCSC markers (e.g., mammosphere formation).
- In vivo studies using xenograft models to evaluate tumor growth inhibition.
Main Results:
- Hsp70 inhibitors significantly reduced TNBC cell viability and proliferation.
- Compounds 1 and 6 effectively inhibited BCSC expansion and mammosphere formation.
- Hsp70 inhibition suppressed BCSCs by down-regulating β-catenin.
- In vivo studies confirmed the tumor suppressive effects of Hsp70 inhibition.
Conclusions:
- Hsp70 inhibitors demonstrate potent anti-BCSC activity in TNBC.
- Targeting Hsp70, potentially via β-catenin modulation, offers a promising therapeutic strategy for TNBC.
- Hsp70 inhibition warrants further investigation as a novel approach to eliminate BCSCs and improve TNBC treatment outcomes.
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