Novel indolyl-chalcones target stathmin to induce cancer cell death
| Autor: | Finith E. Jernigan, Lijun Sun, Yiqiang Wang, Barbara Wegiel, Mailin Li |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Programmed cell death Indoles Biopsy Stathmin Microtubules Small Molecule Libraries 03 medical and health sciences 0302 clinical medicine Chalcones Cell Line Tumor Neoplasms Report medicine Humans Neoplasm Invasiveness Molecular Targeted Therapy Phosphorylation Molecular Biology Mitotic catastrophe Mitosis Gene knockdown biology Cell Death Cell growth Cell Biology Cell biology 030104 developmental biology Mechanism of action 030220 oncology & carcinogenesis Cancer cell biology.protein medicine.symptom Developmental Biology |
| Zdroj: | Cell cycle (Georgetown, Tex.). 15(9) |
| ISSN: | 1551-4005 |
| Popis: | Efficacy of current therapies for advanced and metastatic cancers remains a challenge in clinical practice. We investigated the anti-cancer potency of three novel indoly-chalcones (CITs). Our results indicated the lead molecule CIT-026 (Formula = C20H16FNO) induced cell death in prostate and lung cancer cell lines at sub-micromolar concentration. CITs (CIT-026, CIT-214, CIT-223) lead to microtubule destabilization, cell death and low cell proliferation, which in part was dependent on stathmin (STMN1) expression. Knockdown of STMN1 with siRNA against STMN1 in part restored viability of cancer cells in response to CITs. Further, CIT-026 and CIT-223 blocked cancer cell invasion through matrigel-coated chambers. Mechanistically, CITs inhibited phosphorylation of STMN1 leading to STMN1 accumulation and mitotic catastrophe. In summary, we have identified novel anti-cancer CIT molecules and defined their mechanism of action in vitro. |
| Databáze: | OpenAIRE |
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