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Title: Ribosome biogenesis mediates antitumor activity of flavopiridol in CD44(+)/CD24(-) breast cancer stem cells
Authors: Erol, Ayşe
Acikgöz, Eda
Güven, Ümmü
Düzağaç, Fahriye
Türkkanı, Ayten
Çölçimen, Neşe
Öktem, Gülperi
Keywords: Flavopiridol
ribosome biogenesis
breast cancer stem cell
Issue Date: Dec-2017
Publisher: Spandidos Publications
Source: Erol, A., Acikgoz, E., Guven, U., Duzagac, F., Turkkani, A., Colcimen, N., & Oktem, G. (2017). Ribosome biogenesis mediates antitumor activity of flavopiridol in CD44+/CD24?breast cancer stem cells. Oncology letters, 14(6), 6433-6440.
Abstract: Flavopiridol is a synthetically produced flavonoid that potently inhibits the proliferation of human tumor cell lines. Flavopiridol exerts strong antitumor activity via several mechanisms, including the induction of cell cycle arrest and apoptosis, and the modulation of transcriptional regulation. The aim of the present study was to determine the effect of flavopiridol on a subpopulation of cluster of differentiation (CD)44(+)/CD24(-) human breast cancer MCF7 stem cells. The CD44(+)/CD24(-) cells were isolated from the MCF7 cell line by fluorescence-activated cell sorting and treated with 100, 300, 500, 750 and 1,000 nM flavopiridol for 24, 48 and 72 h. Cell viability and proliferation assays were performed to determine the inhibitory effect of flavopiridol. Gene expression profiling was analyzed using Illumina Human HT-12 v4 Expression BeadChip microarray. According to the results, the half maximal inhibitory concentration (IC50) value of flavopiridol was 500 nM in monolayer cells. Flavopiridol induced growth inhibition and cytotoxicity in breast cancer stem cells (BCSCs) at the IC50 dose. The present study revealed several differentially regulated genes between flavopiridol-treated and untreated cells. The result of the pathway analysis revealed that flavopiridol serves an important role in translation, the ribosome biogenesis pathway, oxidative phosphorylation, the electron transport chain pathway, carbon metabolism and cell cycle. A notable result from the present study is that ribosome-associated gene expression is significantly affected by flavopiridol treatment. The data of the present study indicate that flavopiridol exhibits antitumor activity against CD44(+)/CD24(-) MCF7 BCSCs through different mechanisms, mainly by inhibiting translation and the ribosome biogenesis pathway, and could be an effective chemotherapeutic molecule to target and kill BCSCs.
ISSN: 1792-1074
Appears in Collections:PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Temel Tıp Bilimleri Bölümü / Department of Basic Medical Sciences
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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