Naphthazarin suppresses cell proliferation and induces apoptosis in human colorectal cancer cells via the B-cell lymphoma 2/B-cell associated X protein signaling pathway

Chen, Ai‐Dong; Li, Hui; Li, Yong‐Chun; Zeng, Hai

doi:10.3892/ol.2016.5319

Cited by 6 publications

(5 citation statements)

References 22 publications

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“…Alternatively, compound 9 was inactive in most cell lines, and compound 4 was mostly active in nonhematopoietic adherent cell lines; the remaining compounds exhibited moderate to low activity against most cancer cells. Consistent with our results, naphthazarin (1) 55 has been reported in previous studies to confer cytotoxicity in a variety of cancer cell lines, including SW480, 55 MCF-7, 56 AGS, 57 and A549. 58 Microtubule depolymerization has been shown to be the mechanism for the cytotoxic activity of naphthazarin (1) in A549 cells.…”

Section: ■ Results and Discussionsupporting

confidence: 93%

Identification and Characterization of Natural and Semisynthetic Quinones as Aurora Kinase Inhibitors

et al. 2022

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Aurora kinases (Aurora A, B, and C) are a family of serine/threonine kinases that play critical roles during mitotic initiation and progression. Aurora A and B kinases are ubiquitously expressed, and their overexpression and/or amplification in many cancers have been associated with poor prognosis. Several inhibitors that target Aurora kinases A, B, or both have been developed during the past decade with efficacy in different in vitro and in vivo models for a variety of cancers. Recent studies have also identified Aurora A as a synthetic lethal target for different tumor suppressors, including RB1, SMARCA4, and ARID1A, which signifies the need for Aurora-A-selective inhibitors. Here, we report the screening of a small library of quinones (nine naphthoquinones, one orthoquinone, and one anthraquinone) in a biochemical assay for Aurora A kinase that resulted in the identification of several quinones as inhibitors. IC 50 determination against Aurora A and B kinases revealed the inhibition of both kinases with selectivity toward Aurora A. Two of the compounds, natural quinone naphthazarin (1) and a pseudo anthraquinone, 2-(chloromethyl)quinizarin ( 11), potently inhibited the proliferation of various cancer cell lines with IC 50 values ranging from 0.16 ± 0.15 to 1.7 ± 0.06 and 0.15 ± 0.04 to 6.3 ± 1.8 μM, respectively. Treatment of cancer cells with these compounds for 24 h resulted in abrogated mitosis and apoptotic cell death. Direct binding of both the compounds with Aurora A kinase was also confirmed through STD NMR analysis. Docking studies predicted the binding of both compounds to the ATP binding pocket of Aurora A kinase. We have, therefore, identified quinones as Aurora kinase inhibitors that can serve as a lead for future drug discovery endeavors.

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Section: ■ Results and Discussionsupporting

confidence: 93%

Identification and Characterization of Natural and Semisynthetic Quinones as Aurora Kinase Inhibitors

et al. 2022

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“…The Bcl-2 family plays an important role in the apoptosis of cancer cells; it has proapoptotic protein Bad and anti-apoptotic protein Bcl-2 [ 26 ]. Caspase-3 is one of the most important proteases in the cascade of reactions, and it has been recognized as a target in the design of cancer therapeutics [ 27 ]. PARP is a substrate for caspase-3 and regulates various cellular processes, including DNA repair and apoptosis [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Quinalizarin Induces Apoptosis through Reactive Oxygen Species (ROS)-Mediated Mitogen-Activated Protein Kinase (MAPK) and Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathways in Colorectal Cancer Cells

Wang

Luo

et al. 2018

Med Sci Monit

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BackgroundQuinalizarin (1,2,5,8-tetrahydroxyanthraquinone) exhibits potentially useful anticancer effects by inducing apoptosis in several types of cancer, but its underlying mechanism of action remains unknown. The present study examined the effects of quinalizarin on the induction of cell cycle arrest, apoptosis, the generation of reactive oxygen species (ROS), other underlying mechanisms, and its role in modifying colorectal cancer cell lines.Material/MethodsThe MTT assay was used to evaluate the viability of SW480 and HCT-116 cells that had been treated with quinalizarin and 5-fluorouracil (5-FU). Cell cycle arrest and apoptosis were analyzed by flow cytometry. Western blotting was used to investigate the mitochondrial pathway; Akt, MAPK, and STAT3 signaling pathways were also investigated. The relationship between ROS generation and apoptosis was analyzed by flow cytometry and western blotting.ResultsThe results indicated that quinalizarin significantly inhibits the viability of SW480 and HCT-116 cells in a dose-dependent manner. Quinalizarin induced SW480 cell cycle arrest at G2/M by regulating cyclin B1 and CDK1/2. The apoptosis-related protein expression levels of p-p53, Bad, cleaved caspase-3, cleaved PARP and p-JNK were increased in quinalizarin-treated cells, while protein expression levels Bcl-2, p-Akt, p-ERK, and p-STAT3 were decreased. Quinalizarin induced apoptosis in colorectal cancer cells by regulating MAPK and STAT3 signaling pathways via ROS generation.ConclusionsQuinalizarin induces apoptosis via ROS-mediated MAPK/STAT3 signaling pathways.

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“…Both juglone and plumbagin have shown cytotoxicity to HaCaT keratinocytes, attributed to two different mechanisms, namely, redox cycling and reaction with glutathione (GSH) [ 24 ]. Naphthazarin (5,8-dihydroxynaphthalene-1,4-dione, often also indicated as 5,8-dihydroxy-1,4-naphthoquinone ( 5 ); Figure 2 ), a compound present in the Boraginaceae , Droseraceae , and Nepenthaceae families [ 25 , 26 ], has shown effects on oral squamous cell carcinoma [ 27 ], human breast cancer [ 28 ], human gastric cancer [ 29 ], and human colorectal cancer [ 30 ] cells. Menadione (2-methyl-1,4-naphthoquinone), also known as vitamin K 3 , is a synthetic compound used as a precursor in the synthesis of K 1 and K 2 vitamins and has showed to possess a wide range of biological activities, such as anticancer, antibacterial, antifungal, antimalarial, and anthelmintic activities [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of thia-Michael-Type Adducts between Naphthoquinones and N-Acetyl-L-Cysteine and Their Biological Activity

et al. 2022

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A series of naphthoquinones, namely, 1,4-naphthoquinone, menadione, plumbagin, juglone, naphthazarin, and lawsone, were reacted with N-acetyl-L-cysteine, and except for lawsone, which did not react, the related adducts were obtained. After the tuning of the solvent and reaction conditions, the reaction products were isolated as almost pure from the complex reaction mixture via simple filtration and were fully characterized. Therefore, the aim of this work was to evaluate whether the antitumor activity of new compounds of 1,4-naphthoquinone derivatives leads to an increase in ROS in tumor cell lines of cervical carcinoma (HeLa), neuroblastoma (SH-SY5Y), and osteosarcoma (SaOS2, U2OS) and in normal dermal fibroblast (HDFa). The MTT assay was used to assay cell viability, the DCF-DA fluorescent probe to evaluate ROS induction, and cell-cycle analysis to measure the antiproliferative effect. Compounds 8, 9, and 12 showed a certain degree of cytotoxicity towards all the malignant cell lines tested, while compound 11 showed biological activity at higher IC50 values. Compounds 8 and 11 induced increases in ROS generation after 1 h of exposure, while after 48 h of treatment, only 8 induced an increase in ROS formation in HeLa cells. Cell-cycle analysis showed that compound 8 caused an increase in the number of G0/G1-phase cells in the HeLa experiment, while for the U2OS and SH-SY5Y cell lines, it led to an accumulation of S-phase cells. Therefore, these novel 1,4-naphthoquinone derivatives may be useful as antitumoral agents in the treatment of different cancers.

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Naphthazarin suppresses cell proliferation and induces apoptosis in human colorectal cancer cells via the B-cell lymphoma 2/B-cell associated X protein signaling pathway

Cited by 6 publications

References 22 publications

Identification and Characterization of Natural and Semisynthetic Quinones as Aurora Kinase Inhibitors

Identification and Characterization of Natural and Semisynthetic Quinones as Aurora Kinase Inhibitors

Quinalizarin Induces Apoptosis through Reactive Oxygen Species (ROS)-Mediated Mitogen-Activated Protein Kinase (MAPK) and Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathways in Colorectal Cancer Cells

Synthesis of thia-Michael-Type Adducts between Naphthoquinones and N-Acetyl-L-Cysteine and Their Biological Activity

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