New chalcone-tethered 1,3,5-triazines potentiate the anticancer effect of cisplatin against human lung adenocarcinoma A549 cells by enhancing DNA damage and cell apoptosis

El-Wakil, Marwa H.; Khattab, Sherine N.; El-Yazbi, Amira F.; El-Nikhely, Nefertiti; Soffar, Ahmed; Khalil, Hosam H.

doi:10.1016/j.bioorg.2020.104393

Cited by 29 publications

(10 citation statements)

References 71 publications

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“…Figure 6A,B showed the results obtained by flow cytometry, each histogram was divided into four quadrants, upper left quadrant represented necrotic cells, the upper right quadrant showed late apoptotic cells, lower left quadrant demonstrated viable cells, and lower right quadrant displayed early apoptotic cells. 48 Compared with the control group, the number of late apoptotic cells (upper right quadrant) increased significantly after treatment with 12.5, 25, and 50 μM acrolein, and the total number of apoptotic cells also increased in a dose-dependent manner.…”

Section: Effects Of Acrolein On Cell Apoptosis In Huvecsmentioning

confidence: 86%

Mechanisms of acrolein induces toxicity in human umbilical vein endothelial cells: Oxidative stress, DNA damage response, and apoptosis

Liú

Cheng

Mei

et al. 2021

Environmental Toxicology

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Acrolein is a ubiquitous environmental pollutant that produced by the incomplete combustion of cigarette smoke, forest fires, petroleum fuels, plastic materials, and cooking fumes. Inhalation is a common form of people exposure to acrolein, increasing evidence demonstrates that acrolein impairs the cardiovascular system by targeting vascular endothelial cells. However, the molecular mechanism of the cytotoxicity of acrolein exposure on vascular endothelial cells remains unclear. This work focused on the toxicity of acrolein on human umbilical vein endothelial cells (HUVECs). The molecular mechanism was studied based on oxidative stress, DNA damage response (DDR), and mitochondrial apoptosis pathways. After HUVECs were treated with 12.5, 25, and 50 μM acrolein for 24 h, cell viability, cell colony formation, mitochondrial membrane potential, and adenosine triphosphate content significantly reduced, and acrolein increased intracellular reactive oxygen species, apoptosis rate, and 8-hydroxy-2 deoxyguanosine (8-OHdG) level. Furthermore, p38MAPK and c-Jun N-terminal kinase signaling pathways were activated in response to oxidative stress. Moreover, acrolein induced G0/G1phase arrest, promoted the expression of γ-H2AX, activated the DDR signaling pathway (Ataxia-Telangiectasia-Mutated [ATM] and Rad-3-related/Chk1 and ATM/Chk2), and triggered the consequent cell cycle checkpoints. Finally, the protein expression of Bax/Bcl-2 and cleaved Caspase-3 was up-regulated, suggesting apoptosis was induced by triggering the mitochondrial apoptosis pathway. All these results indicated that acrolein induced HUVECs cytotoxicity by regulating oxidative stress, DNA damage, and apoptosis. This study provides a novel perspective on the mechanism of acrolein-induced cardiovascular toxicity, it will be helpful for the prevention of acrolein-induced cardiovascular disease.

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Section: Effects Of Acrolein On Cell Apoptosis In Huvecsmentioning

confidence: 86%

Mechanisms of acrolein induces toxicity in human umbilical vein endothelial cells: Oxidative stress, DNA damage response, and apoptosis

Liú

Cheng

Mei

et al. 2021

Environmental Toxicology

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“…In addition to their effect on oxidative stress-induced DNA damage, chalcones can cause DNA damage by binding DNA strands through van der Waal forces and aromatic ring stacking interactions. The unsaturated carbonyl system in chalcone compounds supports stronger electrostatic interactions between the hydrogen and DNA bases, as evidenced via molecular docking experiments showing that chalcones are bound to a DNA dodecamer with many hydrogen bonds (El-Wakil et al 2020 ). This may further explain DNA damage induction by chalcone derivatives.…”

Section: Discussionmentioning

confidence: 98%

[1,2,4] Triazolo [3,4-a]isoquinoline chalcone derivative exhibits anticancer activity via induction of oxidative stress, DNA damage, and apoptosis in Ehrlich solid carcinoma-bearing mice

WalyEldeen

El-Shorbagy

Hassaneen

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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Despite the advances made in cancer therapeutics, their adverse effects remain a major concern, putting safer therapeutic options in high demand. Since chalcones, a group of flavonoids and isoflavonoids, act as promising anticancer agents, we aimed to evaluate the in vivo anticancer activity of a synthetic isoquinoline chalcone (CHE) in a mice model with Ehrlich solid carcinoma. Our in vivo pilot experiments revealed that the maximum tolerated body weight-adjusted CHE dose was 428 mg/kg. Female BALB/c mice were inoculated with Ehrlich ascites carcinoma cells and randomly assigned to three different CHE doses administered intraperitoneally (IP; 107, 214, and 321 mg/kg) twice a week for two consecutive weeks. A group injected with doxorubicin (DOX; 4 mg/kg IP) was used as a positive control. We found that in CHE-treated groups: (1) tumor weight was significantly decreased; (2) the total antioxidant concentration was substantially depleted in tumor tissues, resulting in elevated oxidative stress and DNA damage evidenced through DNA fragmentation and comet assays; (3) pro-apoptotic genes p53 and Bax, assessed via qPCR, were significantly upregulated. Interestingly, CHE treatment reduced immunohistochemical staining of the proliferative marker ki67, whereas BAX was increased. Notably, histopathological examination indicated that unlike DOX, CHE treatment had minimal toxicity on the liver and kidney. In conclusion, CHE exerts antitumor activity via induction of oxidative stress and DNA damage that lead to apoptosis, making CHE a promising candidate for solid tumor therapy.

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“…In their study, Khattab and colleagues synthesized chalcone-tethered 1,3,5-triazines and assessed their anti-cancer potential. [41] The MTT assay revealed that hybrids 81 and 82 exhibited significant inhibition of A549 cancer cell viability, with IC 50 values of 24. Ari and his research group reported synthesis of novel chalcone derivative, [(2E,4E)-1-(7-ethoxy-1-benzofuran-2-yl)-5-(4-hydroxy-3-methoxyphenyl)penta-2,4-dien-1-one] 81 a and evaluated the anticancer potential on human lung (A549, H1299) and colon cancer (HCT116, HT29) cells.…”

Section: Chalcones As Anti-cancer Agentsmentioning

confidence: 99%

Chalcones: Effective Agents for Fighting Cancer Across Multiple Cell Lines

Kaur,

Anand

et al. 2024

ChemistrySelect

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This review article explores the mushrooming research on chalcone hybrid molecules as promising anticancer agents. Chalcones, featuring a unique chemical structure, exhibit diverse biological activities, including potent anticancer properties. Various synthetic chalcones and their derivatives have demonstrated remarkable efficacy against different cancer cell lines, offering advantages such as reduced mutagenicity. The article summarizes recent advancements in chalcone hybrid research, highlighting their potential in cancer treatment and paving the way for novel, safer, and more effective chemotherapeutic agents.

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New chalcone-tethered 1,3,5-triazines potentiate the anticancer effect of cisplatin against human lung adenocarcinoma A549 cells by enhancing DNA damage and cell apoptosis

Cited by 29 publications

References 71 publications

Mechanisms of acrolein induces toxicity in human umbilical vein endothelial cells: Oxidative stress, DNA damage response, and apoptosis

Mechanisms of acrolein induces toxicity in human umbilical vein endothelial cells: Oxidative stress, DNA damage response, and apoptosis

[1,2,4] Triazolo [3,4-a]isoquinoline chalcone derivative exhibits anticancer activity via induction of oxidative stress, DNA damage, and apoptosis in Ehrlich solid carcinoma-bearing mice

Chalcones: Effective Agents for Fighting Cancer Across Multiple Cell Lines

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