Flavopiridol Suppresses Cell Proliferation and Migration and Induces Apoptotic Cell Death by Inhibiting Oncogenic FOXM1 Signaling in IDH Wild-Type and IDH-Mutant GBM Cells
Guler A. Hamurcu Z. Ulutabanca H. Cınar V. Nurdinov N. Erdem S. Ozpolat B.
February 2024Springer
Molecular Neurobiology
2024#61Issue 21061 - 1079 pp.
Glioblastoma multiforme (GBM) remains one of the most challenging solid cancers to treat due to its highly aggressive and drug-resistant nature. Flavopiridol is synthetic flavone that was recently approved by the FDA for the treatment of acute myeloid leukemia. Flavopiridol exhibits antiproliferative activity in several solid cancer cells and currently evaluated in clinical trials in several solid and hematological cancers. In this study, we investigated the molecular mechanisms underlying antiproliferative effects of flavopiridol in GBM cell lines with wild-type and mutant encoding isocitrate dehydrogenase 1 (IDH1). We found that flavopiridol inhibits proliferation, colony formation, and migration and induces apoptosis in IDH1 wild-type and IDH-mutant cells through inhibition of FOXM1 oncogenic signaling. Furthermore, flavopiridol treatment also inhibits of NF-KB, mediators unfolded protein response (UPR), including, GRP78, PERK and IRE1α, and DNA repair enzyme PARP, which have been shown to be potential therapeutic targets by downregulating FOXM1 in GBM cells. Our findings suggest for the first time that flavopiridol suppresses proliferation, survival, and migration and induces apoptosis in IDH1 wild-type and IDH1-mutant GBM cells by targeting FOXM1 oncogenic signaling which also regulates NF-KB, PARP, and UPR response in GBM cells. Flavopiridol may be a potential novel therapeutic strategy in the treatment of patients IDH1 wild-type and IDH1-mutant GBM.
Apoptosis , Flavopiridol , FOXM1 , GBM , IDH1 mutation , NF-kB
Text of the article Перейти на текст статьи
Department of Medical Biology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
Betül-Ziya Eren Genome and Stem Cell Center, Erciyes University, Kayseri, Turkey
Department of Neurosurgery, Faculty of Medicine, Erciyes University, Kayseri, Turkey
Faculties of Medicine and Dentistry, Ahmet Yesevi University, Turkestan, Kazakhstan
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, United States
Methodist Neil Cancer Center, Houston, TX, United States
Department of Medical Biology
Betül-Ziya Eren Genome and Stem Cell Center
Department of Neurosurgery
Faculties of Medicine and Dentistry
Department of Nanomedicine
Methodist Neil Cancer Center
10 лет помогаем публиковать статьи Международный издатель
Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026