2-(3-Methoxyphenyl)-5-methyl-1,8-naphthyridin-4(1H)-one (HKL-1) induces G2/M arrest and mitotic catastrophe in human leukemia HL-60 cells

Hsu, Mei‐Hua; Liu, Chin Yu; Lin, Chiao Min; Chen, Yen Jung; Chen, Chun‐Jen; Lin, Yu; Huang, Li Jiau; Lee, Kuo Hsiung̀; Kuo, Sheng Chu

doi:10.1016/j.taap.2011.12.026

Cited by 14 publications

(2 citation statements)

References 23 publications

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“…In leukemia, attention has already been devoted to antimitotic agents. For example, in HL-60 cells, the antimitotic agent HKL-1 was found to evoke mitotic catastrophes by downregulating the mitotic stage-specific kinase CENPE and downregulating Bcl-2 ( 18 ). Moreover, an anti-mitogenic agent GSK923295A, capable of inhibiting CENPE motility activity, exhibited substantial remission-inducing antileukemia activities towards acute lymphoblastic leukemia (ALL) xenografts ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia

Shi

Niu

et al. 2021

Front. Oncol.

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The prognosis of chemoresistant acute myeloid leukemia (AML) is still poor, mainly owing to the sustained proliferation ability of leukemic cells, while the microtubules have a major role in sustaining the continuity of cell cycle. In the present study, we have identified CENPE, a microtubular kinesin-like motor protein that is highly expressed in the peripheral blood of patients with chemoresistant AML. In our in vitro studies, knockdown of CENPE expression resulted in the suppression of proliferation of myeloid leukemia cells and reversal of cytarabine (Ara-C) chemoresistance. Furthermore, Lin28A, one of the RNA-binding oncogene proteins that increase cell proliferation and invasion and contribute to unfavorable treatment responses in certain malignancies, was found to be remarkably correlated with CENPE expression in chemoresistance AML. Overexpression of LIN28A promoted the proliferation and Ara-C chemoresistance of leukemic cells. RIP assay, RNA pull-down, and dual luciferase reporter analyses indicated that LIN28A bound specifically to the promoter region GGAGA of CENPE. In addition, the impacts of LIN28A on cell growth, apoptosis, cell cycle progression, and Ara-C chemoresistance were reverted by the knockdown of CENPE. Hence, Lin28A/CENPE has enhanced the proliferation and chemoresistance of AML, and therefore, it could be a prospective candidate for AML treatment.

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Section: Introductionmentioning

confidence: 99%

Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia

Shi

Niu

et al. 2021

Front. Oncol.

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“…In the Western blot analysis, a marked decrease in the expressions of cyclin B1 and CDK1 were detected in HL-60 cells. 32,33 As shown in Figure 6, compound 12e induced a transient increase followed by a decrease in cyclin B1 protein expression, whereas CDK1 protein expression level decreased in a concentration-dependent manner in HL-60 cells (Fig. 6A).…”

Section: Biological Evaluationmentioning

confidence: 82%

Design and synthesis of 6,7-methylenedioxy-4-substituted phenylquinolin-2(1H)-one derivatives as novel anticancer agents that induce apoptosis with cell cycle arrest at G2/M phase

Chen

Lin

Huang

et al. 2013

Bioorganic & Medicinal Chemistry

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Novel 6,7-methylenedioxy-4-substituted phenylquinolin-2-one derivatives 12a–n were designed and prepared through an intramolecular cyclization reaction and evaluated for in vitro anticancer activity. Among the synthesized compounds, 6,7-methylenedioxy-4-(2,4-dimethoxyphenyl)quinolin-2(1H)-one (12e) displayed potent cytotoxicity against several different tumor cell lines at a sub-micromolar level. Furthermore, results of fluorescence-activated cell sorting (FACS) analysis suggested that 12e induced cell cycle arrest in the G2/M phase accompanied by apoptosis in HL-60 and H460 cells. This action was confirmed by Hoechst staining and caspase-3 activation. Due to their easy synthesis and remarkable biological activities, 4-phenylquinolin-2(1H)-one analogs (4-PQs) are promising new anticancer leads based on the quinoline scaffold. Accordingly, compound 12e was identified as a new lead compound that merits further optimization and development as an anticancer candidate.

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Mitotic Catastrophe

Souza

Ayub

Yip

2018

Apoptosis and Beyond

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2-(3-Methoxyphenyl)-5-methyl-1,8-naphthyridin-4(1H)-one (HKL-1) induces G2/M arrest and mitotic catastrophe in human leukemia HL-60 cells

Cited by 14 publications

References 23 publications

Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia

Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia

Design and synthesis of 6,7-methylenedioxy-4-substituted phenylquinolin-2(1H)-one derivatives as novel anticancer agents that induce apoptosis with cell cycle arrest at G2/M phase

Mitotic Catastrophe

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