Michalski, Marlen and Bauer, Magdalena and Walz, Franziska and Tuemen, Deniz and Heumann, Philipp and Stoeckert, Petra and Gunckel, Manuela and Kunst, Claudia and Kandulski, Arne and Schmid, Stephan and Mueller, Martina and Guelow, Karsten (2023) Simultaneous Inhibition of Mcl-1 and Bcl-2 Induces Synergistic Cell Death in Hepatocellular Carcinoma. BIOMEDICINES, 11 (6): 1666. ISSN , 2227-9059
Full text not available from this repository. (Request a copy)Abstract
Despite the recent approval of new therapies, the prognosis for patients with hepatocellular carcinoma (HCC) remains poor. There is a clinical need for new highly effective therapeutic options. Here, we present a combined application of BH3-mimetics as a potential new treatment option for HCC. BH3-mimetics inhibit anti-apoptotic proteins of the BCL-2 family and, thus, trigger the intrinsic apoptosis pathway. Anti-apoptotic BCL-2 proteins such as Bcl-2 and Mcl-1 are frequently overexpressed in HCC. Therefore, we analyzed the efficacy of the two BH3-mimetics ABT-199 (Bcl-2 inhibitor) and MIK665 (Mcl-1 inhibitor) in HCC cell lines with differential expression levels of endogenous Bcl-2 and Mcl-1. While administration of one BH3-mimetic alone did not substantially trigger cell death, the combination of two inhibitors enhanced induction of the intrinsic apoptosis pathway. Both drugs acted synergistically, highlighting the effectivity of this specific BH3-mimetic combination, particularly in HCC cell lines. These results indicate the potential of combining inhibitors of the BCL-2 family as new therapeutic options in HCC.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BH3-ONLY PROTEINS; HEPATOMA-CELLS; VENETOCLAX; CANCER; APOPTOSIS; MITOCHONDRIA; SENSITIVITY; DEPENDENCY; MECHANISMS; PATHWAYS; hepatocellular carcinoma (HCC); apoptosis; BH3-mimetics; ABT-199; venetoclax; MIK665; S64315 |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Mar 2024 13:04 |
| Last Modified: | 10 Mar 2024 13:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59566 |
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