Chalcone HTMC causes in vitro selective cytotoxicity, cell-cycle G1 phase arrest through p53-dependent pathway in human lung adenocarcinoma A549 cells, and in vivo tumor growth suppression

Rao, Yerra Koteswara; Kao, Te-Yu; Ko, Jiunn‐Liang; Tzeng, Yew‐Min

doi:10.1016/j.bmcl.2010.09.056

Cited by 31 publications

(10 citation statements)

References 24 publications

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“…In A549 cells, it induced G1 cell cycle arrest and upregulated tumor suppresser genes p21 and p53 and downregulated cell-cycle regulatory proteins phosphorylation of cdc2 (Tyr 15 and Tyr 161 ) and Rb (Ser 795 and Ser 807/811 ), which may be one of its molecular mechanisms. In addition, in vivo data demonstrated that this chalcone acted as a tumor growth suppressing agent [118]. …”

Section: Mechanisms Of Antitumor Activitymentioning

confidence: 99%

An Update on Antitumor Activity of Naturally Occurring Chalcones

Zhang

Wang

Guo

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades.

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Section: Mechanisms Of Antitumor Activitymentioning

confidence: 99%

An Update on Antitumor Activity of Naturally Occurring Chalcones

Zhang

Wang

Guo

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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“…Chalcones, a class of open-chain flavonoids, can not only be biosynthesized by plants, but can also be synthetically manufactured [ 4 , 5 ]. Different plant-derived forms of chalcone have been isolated that contain several substitutive patterns, including hydroxy, methyl, and methoxy substituents on both of the aromatic rings [ 6 , 7 , 8 , 9 , 10 , 11 ]. However, halogen-containing chalcone derivatives are rare in the plant kingdom [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

2-Bromo-4′-methoxychalcone and 2-Iodo-4′-methoxychalcone Prevent Progression of Hyperglycemia and Obesity via 5′-Adenosine-Monophosphate-Activated Protein Kinase in Diet-Induced Obese Mice

Hsieh

Chang

Tsai

et al. 2018

IJMS

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Obesity and diabetes are global health-threatening issues. Interestingly, the mechanism of these pathologies is quite different among individuals. The discovery and development of new categories of medicines from diverse sources are urgently needed for preventing and treating diabetes and other metabolic disorders. Previously, we reported that chalcones are important for preventing biological disorders, such as diabetes. In this study, we demonstrate that the synthetic halogen-containing chalcone derivatives 2-bromo-4′-methoxychalcone (compound 5) and 2-iodo-4′-methoxychalcone (compound 6) can promote glucose consumption and inhibit cellular lipid accumulation via 5′-adenosine-monophosphate-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase 1 (ACC) phosphorylation in 3T3-L1 adipocytes and C2C12 skeletal myotubes. In addition, the two compounds significantly prevented body weight gain and impaired glucose tolerance, hyperinsulinemia, and insulin resistance, which collectively help to delay the progression of hyperglycemia in high-fat-diet-induced obese C57BL/6 mice. These findings indicate that 2-bromo-4′-methoxychalcone and 2-iodo-4′-methoxychalcone could act as AMPK activators, and may serve as lead compounds for a new class of medicines that target obesity and diabetes.

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“…Chalcone derivatives have various biological properties including anti-inflammatory, antioxidant, and cytoprotective activities in normal cells (Kachadourian et al, 2012;Park et al, 2009;Szliszka et al, 2010;Vogel et al, 2010). It has also been demonstrated that chalcone derivatives have anti-cancer activity through ROS production in various tumor cells (Kim et al, 2010), as well as potent cytotoxic activity in carcinoma cells (Rao et al, 2010). Although chalcone derivatives have very similar chemical structures, their cellular activities are quite different; they can act as chemopreventors or chemosensitizers depending on their structure and cell type (Yadav et al, 2011) .…”

Section: Introductionmentioning

confidence: 99%

4-Methoxychalcone Enhances Cisplatin-Induced Oxidative Stress and Cytotoxicity by Inhibiting the Nrf2/ARE-Mediated Defense Mechanism in A549 Lung Cancer Cells

Lim

Lee

Cho

et al. 2013

Molecules and Cells

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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator for the protection of cells against oxidative and xenobiotic stresses. Recent studies have demonstrated that high constitutive expression of Nrf2 is observed in many types of cancer cells showing resistance to anti-cancer drugs, suggesting that the suppression of overexpressed Nrf2 could be an attractive therapeutic strategy to overcome cancer drug resistance. In the present study, we aimed to find small molecule compounds that enhance the sensitivity of tumor cells to cisplatin induced cytotoxicity by suppressing Nrf2-mediated defense mechanism. A549 lung cancer cells were shown to be more resistant to the anti-cancer drug cisplatin than HEK293 cells, with higher Nrf2 signaling activity; constitutively high amounts of Nrf2-downstream target proteins were observed in A549 cells. Among the three chalcone derivatives 4-methoxy-chalcone (4-MC), hesperidin methylchalcone, and neohesperidin dihydrochalcone, 4-MC was found to suppress transcriptional activity of Nrf2 in A549 cells but to activate it in HEK293 cells. 4-MC was also shown to down-regulate expression of Nrf2 and the downstream phase II detoxifying enzyme NQO1 in A549 cells. The PI3K/Akt pathway was found to be involved in the 4-MC-induced inhibition of Nrf2/ARE activity in A549 cells. This inhibition of Nrf2 signaling results in the accelerated generation of reactive oxygen species and exacerbation of cytotoxicity in cisplatin-treated A549 cells. Taken together, these results suggest that the small molecule compound 4-MC could be used to enhance the sensitivity of tumor cells to the therapeutic effect of cisplatin through the regulation of Nrf2/ARE signaling.

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Chalcone HTMC causes in vitro selective cytotoxicity, cell-cycle G1 phase arrest through p53-dependent pathway in human lung adenocarcinoma A549 cells, and in vivo tumor growth suppression

Cited by 31 publications

References 24 publications

An Update on Antitumor Activity of Naturally Occurring Chalcones

An Update on Antitumor Activity of Naturally Occurring Chalcones

2-Bromo-4′-methoxychalcone and 2-Iodo-4′-methoxychalcone Prevent Progression of Hyperglycemia and Obesity via 5′-Adenosine-Monophosphate-Activated Protein Kinase in Diet-Induced Obese Mice

4-Methoxychalcone Enhances Cisplatin-Induced Oxidative Stress and Cytotoxicity by Inhibiting the Nrf2/ARE-Mediated Defense Mechanism in A549 Lung Cancer Cells

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