Flubendazole elicits anti‐metastatic effects in triple‐negative breast cancer via STAT3 inhibition
| العنوان: | Flubendazole elicits anti‐metastatic effects in triple‐negative breast cancer via STAT3 inhibition |
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| المؤلفون: | Jae Hong Seo, Seojin Jang, Hyunsook An, Daeil Sung, Ji Young Kim, Yoon Jae Kim, Tae Min Cho, Lee Farrand, Eunhye Oh |
| المصدر: | International Journal of Cancer. 143:1978-1993 |
| بيانات النشر: | Wiley, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | STAT3 Transcription Factor, 0301 basic medicine, Cancer Research, Lung Neoplasms, Angiogenesis, Apoptosis, Triple Negative Breast Neoplasms, Flubendazole, Metastasis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Antigens, CD, Cancer stem cell, Cell Line, Tumor, Humans, Medicine, Neoplasm Metastasis, STAT3, Triple-negative breast cancer, Cell Proliferation, biology, business.industry, Liver Neoplasms, Cancer, medicine.disease, G2 Phase Cell Cycle Checkpoints, Mebendazole, 030104 developmental biology, Oncology, chemistry, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Cancer research, biology.protein, Female, business |
| الوصف: | Tumor metastasis remains the cause of 90% of cancer-related deaths. Cancer stem cells (CSC) are thought to be responsible for the aggressive and metastatic nature of triple-negative breast cancers (TNBC), and new therapeutic strategies are being devised to target them. Flubendazole (FLU) is a widely used anthelmintic agent that also exhibits anticancer activity in several cancer types. The aim of this study was to characterize the mechanism of action of FLU on breast cancer stem cell (BCSC)-like properties and metastasis in TNBC. FLU treatment caused a significant induction of apoptosis, accompanied by G2/M phase accumulation, caspase-3/-7 activation and the dysregulation of STAT3 activation in TNBC cells. The latter phenomenon was associated with impairment of cancer stem-like traits, concomitant with a reduction in the CD24low /CD44high , CD24high /CD49fhigh subpopulation, ALDH1 activity and mammosphere formation. The BCSC-enriched populations exhibited enhanced metastasis with higher STAT3 activation, while FLU administration inhibited tumor growth, angiogenesis and lung and liver metastasis, coinciding with decreased MMP-2 and MMP-9 levels in circulating blood. FLU kills not only rapid proliferating tumor cells but also effectively eradicates BCSC-like cells in vitro and in vivo. Our findings warrant further investigation of FLU as a treatment for metastatic TNBC. |
| تدمد: | 1097-0215 0020-7136 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fb044b9b65445a02d7be0816f70ebb01 https://doi.org/10.1002/ijc.31585 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fb044b9b65445a02d7be0816f70ebb01 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970215 00207136 |
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