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. 2024 May 30;15(1):197.
doi: 10.1007/s12672-024-01063-4.

Bestatin attenuates breast cancer stemness by targeting puromycin-sensitive aminopeptidase

Yan Ma #  1 , Xintong Yang #  1 , Pengge Pan  1 , Jinyi Yang  1 , Xiaojuan Wu  2 , Danhan Wang  3 , Hui Gao  4
Affiliations

Bestatin attenuates breast cancer stemness by targeting puromycin-sensitive aminopeptidase

Yan Ma et al. Discov Oncol. .

Abstract

Breast cancer is a prevalent malignant tumor among women with an increasing incidence rate annually. Breast cancer stem cells (BCSCs) are integral in impeding tumor advancement and addressing drug resistance. Bestatin serves as an adjuvant chemotherapy, triggering apoptosis in cancer cells. In this study, the effects of bestatin on sorted BCSCs from breast cancer cell lines have been studied. Our results indicated that bestatin inhibits the migration and proliferation of breast cancer cells by reducing the stemness of BCSCs both in vitro and in vivo. Puromycin-sensitive aminopeptidase is implicated in the process through the regulation of cell cycle, resulting in heightened cell apoptosis and diminished cell proliferation of BCSCs. Our study suggest that targeting cancer stem cell may offer a promising approach in breast cancer treatment, presenting noval therapeutic strategies for patients with breast cancer.

Keywords: Apoptosis; Bestatin; Breast cancer; Breast cancer stem cells; Proliferation; Puromycin-sensitive aminopeptidase.

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Conflict of interest statement

The authors have no competing interests.

Figures

Fig. 1
Fig. 1
Effects of bestatin on migration, proliferation and cell cycles for MCF-7 and SKBR3 breast cancer cell lines. A A dose–response curve for bestatin in MCF-7 and SKBR3 cells. B–D Wound healing assays were conducted to investigate the influence of bestatin on cell migration capabilities. E–G Representative images and statistical analysis of colony formation of breast cancer cells upon bestatin treatment. H–J Representative images and statistical analysis of cell cycle profiles upon bestatin treatment. Each value represents mean ± S.D from separate experiments
Fig. 2
Fig. 2
Effects of bestatin on the stemness of breast cancer stem cells. A ALDH activities breast cancer cells treated with or without specific ALDH inhibitor diethylaminobenzaldehyde (DEAB) were analyzed by flow cytometry. B–C Representative images and statistical analysis of the sphere formed by BCSCs sorted from MCF-7 and SKBR3 breast cancer cells. D–E Representative images and statistical analysis of 3Ds formed by BCSCs sorted from MCF-7 and SKBR3 breast cancer cells. Each value represents mean ± S.D from separate experiments
Fig. 3
Fig. 3
Effects of bestatin on PSA, PCNA and cleaved-Caspase3 expression of spheres formed by breast cancer stem cells. A–B Immunofluoresence staining and statistical analysis of PSA in control and bestatin-treated BCSC-formed spheres. C–D Immunofluoresence staining and statistical analysis of PCNA in control and bestatin-treated BCSC-formed spheres. E–F Immunofluoresence staining and statistical analysis of cleaved-Caspase3 in control and bestatin-treated BCSC-formed spheres. Each value represents mean ± S.D from separate experiments
Fig. 4
Fig. 4
Relationship between PSA expression and breast cancer. A Decreased expression of PSA indicated poor prognosis (Overall survival) and RFS (Recurrence free survival) in gene and protein level. B The results of Immunohistochemistry between normal and breast cancer tissues. C Differential expression of PSA between tumor and normal tissues. D–E Differential expression levels of PSA gene in different subtypes of breast cancers
Fig. 5
Fig. 5
Effects of bestatin on tumorigenesis of BCSCs in vivo. A–B The images and statistical analysis of tumors derived from BCSCs treated with or without bestatin. C–D The images and statistical analysis of lung metastasis from the xenografted mice. E Immunohistochemistry staining and statistical analysis of PSA, Ki67 and cleaved-Caspase3 in control and bestatin-treated BCSC-formed spheres
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References

    1. Riggio AI, Varley KE, Welm AL. The lingering mysteries of metastatic recurrence in breast cancer. Br J Cancer. 2021;124(1):13–26. doi: 10.1038/s41416-020-01161-4. - DOI - PMC - PubMed
    1. Kashyap D, et al. Global increase in breast cancer incidence: risk factors and preventive measures. Biomed Res Int. 2022;2022:9605439. doi: 10.1155/2022/9605439. - DOI - PMC - PubMed
    1. Artignan J, et al. Are breast cancer patients with suboptimal adherence to cardiovascular treatment more likely to discontinue adjuvant endocrine therapy? Competing risk survival analysis in a nationwide cohort of postmenopausal women. BMC Med. 2023;21(1):463. doi: 10.1186/s12916-023-03156-3. - DOI - PMC - PubMed
    1. Valenza C, et al. Primary malignant phyllodes tumors of the breast: a retrospective analysis from a referral center. Eur J Cancer. 2023;196:113423. doi: 10.1016/j.ejca.2023.113423. - DOI - PubMed
    1. Ji J, et al. Falls prechemotherapy and toxicity-related hospitalization during adjuvant chemotherapy for breast cancer in older women: results from the prospective multicenter HOPE trial. Cancer. 2023 doi: 10.1002/cncr.35105. - DOI - PMC - PubMed

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