Response of Myeloid Leukemia Cells to Luteolin is Modulated by Differentially Expressed Pituitary Tumor-Transforming Gene 1 (PTTG1) OncoproteinD

doi:10.3390/ijms19041173

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Title:	Response of Myeloid Leukemia Cells to Luteolin is Modulated by Differentially Expressed Pituitary Tumor-Transforming Gene 1 (PTTG1) OncoproteinD
Authors:	Chen, Pei-Yi Tien, Hsin-Jung Chen, Shih-Fen Horng, Chi-Ting Tang, Huei-Lin Jung, Hui-Ling Wu, Ming-Jiuan Yen, Jui-Hung
Contributors:	Buddhist Tzu Chi Gen Hosp, Ctr Med Genet Tzu Chi Univ, Dept Mol Biol & Human Genet Kaohsiung Armed Force Gen Hosp, Dept Ophthalmol Kaohsiung Armed Force Gen Hosp, Dept Pharm Chia Nan Univ Pharm & Sci, Dept Biotechnol
Keywords:	luteolin PTTG1 myeloid leukemia cells apoptosis cell proliferation
Date:	2018-04
Issue Date:	2019-11-15 15:46:14 (UTC+8)
Publisher:	MDPI
Abstract:	Luteolin, a flavonoid nutraceutical abundant in vegetables and fruits, exhibits a wide range of bioactive properties, including antioxidant, anti-inflammatory and anti-cancer activities. Pituitary tumor-transforming gene 1 (PTTG1), an oncoprotein that regulates cell proliferation, is highly expressed in several types of cancer cells including leukemia. In this study, we aim to investigate the anti-cancer effects of luteolin on cells with differential PTTG1 expression and their underlying mechanisms in human myeloid leukemia cells. Methyl thiazolyl tetrazolium (MTT) assay data showed that luteolin (25-100 mu M) significantly reduced cell viability in THP-1, HL-60 and K562 cells but did not affect normal peripheral blood mononuclear cells (PBMCs). Flow cytometric analysis and Western blot data demonstrated that luteolin induced a stronger apoptosis on undifferentiated myeloid leukemia cells with higher PTTG1 protein levels than on 12-myristate 13-acetate (PMA)- or all-trans-retinoic acid (ATRA)-differentiated cells with lower PTTG1 expression. Furthermore, PTTG1 knockdown by shRNA in leukemia cells suppressed cell proliferation, arrested cell-cycle progression and impaired the effectiveness of luteolin on cell-cycle regulation. Moreover, PTTG1-knockdown cells with luteolin exposure presented a reduction of the apoptotic proteins and maintained higher levels of the anti-apoptotic proteins such as Mcl-1, Bcl-2 and p21, which exhibited greater resistance to apoptosis. Finally, microarray analysis showed that 20 genes associated with cell proliferation, such as CXCL10, VEGFA, TNF, TP63 and FGFR1, were dramatically down-regulated in PTTG1-knockdown cells. Our current findings clearly demonstrate that luteolin-triggered leukemic cell apoptosis is modulated by the differential expression of the PTTG1. PTTG1 oncoprotein overexpression may modulate cell proliferation-related regulators and enhance the response of myeloid leukemia cells to luteolin. Luteolin is beneficial for the treatment of cancer cells with highly expressed PTTG1 oncoprotein.
???metadata.dc.relation.uri???:	http://dx.doi.org/10.3390/ijms19041173
Relation:	Molecules, v.19, n.4, 1173
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Periodical Articles

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