Verticillin A increases the BIMEL/MCL-1 ratio to overcome ABT-737-resistance in human colon cancer cells by targeting the MEK/ERK pathway
In: Biochemical and Biophysical Research Communications, Jg. 567 (2021-08-01), S. 22-28
Online
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Zugriff:
ABT-737, a small molecule BH-3 mimetic, is less effective against human colon cancers due to its resistance. Verticillin A is a natural compound, which was previously purified from verticillium-infected mushrooms. Hence, we aimed at overcoming the ABT737 resistance observed in CRC tumors by combining Verticillin A with ABT-737 and figuring out the potential mechanism. In this study, we observed that Verticillin A could sensitize colon cancer to ABT-737-induced cell death through induction of mitochondrial-dependent apoptosis. Verticillin A could significantly increase the BIMEL/MCL-1 ratio to overcome ABT737 resistance through the suppression of the MEK/ERK pathway. In addition, up-regulation of BIM protein levels to activate BAX translocation results in apoptosis induction. Altogether, our work suggested the potential application of Verticillin A as a MEK inhibitor in BH3-mimetic-based therapy.
| Titel: |
Verticillin A increases the BIMEL/MCL-1 ratio to overcome ABT-737-resistance in human colon cancer cells by targeting the MEK/ERK pathway
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| Autor/in / Beteiligte Person: | Huang, Qiqian ; Tu, Kai ; Liu, Feiyan ; Guan, Yuelin |
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| Zeitschrift: | Biochemical and Biophysical Research Communications, Jg. 567 (2021-08-01), S. 22-28 |
| Veröffentlichung: | Elsevier BV, 2021 |
| Medientyp: | unknown |
| ISSN: | 0006-291X (print) |
| DOI: | 10.1016/j.bbrc.2021.05.103 |
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