Apoptosis: A target for anticancer therapy with novel cyanopyridines

Ismail, Magda M. F.; Farrag, Ayman A.; Harras, Marwa F.; Ibrahim, Mona H.; Mehany, Ahmed B. M.

doi:10.1016/j.bioorg.2019.103481

Cited by 39 publications

(33 citation statements)

References 43 publications

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“…It can be seen from the Table5that parameters obtained for the both structures, 7 and 7a, fit the Lipinski's rule. Furthermore, absorption was calculated[53], and the obtained values were within the range of 46.53-64.21% which demonstrated that synthesized compounds have adequate cell membrane permeability and bioavailability. The number of rotatable bonds is another important parameter which is associated with good bioavailability.…”

mentioning

confidence: 73%

“…The pharmacokinetics parameters, such as blood brain barrier permeability, the ability of a compound to be the P-gp (permeability glycoprotein) substrate and CYP (cytochrome enzymes) inhibitor, were analyzed (Table S2, Supplementary material). All investigated compounds have shown no permeation to the blood brain barrier, thus side effects to the central nervous system are prevented [53]. The P-gp is a key player in the process of an active efflux through biological membranes, and along with the CYPs it participates in the excretion processes [55].…”

Section: In Silico Assessment Of Physicochemical and Adme Propertiesmentioning

confidence: 99%

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Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity

et al. 2021

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mentioning

confidence: 73%

Section: In Silico Assessment Of Physicochemical and Adme Propertiesmentioning

confidence: 99%

Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity

et al. 2021

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“…Once apoptosis occurs, BAX will translocate to the mitochondria to increase mitochondrial membrane permeability, resulting in the release of cytochrome c and other pro-apoptotic factors into the cytoplasm and activation of caspases-3. 30,32,33 A similar process could be detected in the mitochondrial-mediated platelet apoptosis in a hypertension environment. First, flow cytometry data showed that hypertension could enhance the PS eversion of platelets, whereas GsMTx-4 treatment could inhibit it (Figure 4E).…”

Section: Inhibition Piezo1 Ameliorates Mitochondrial Dysfunction and ...mentioning

confidence: 60%

Piezo1 initiates platelet hyperreactivity and accelerates thrombosis in hypertension

Zhao

Wei

Xin

et al. 2021

Journal of Thrombosis and Haemostasis

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Background Thrombosis is the pathological basis of cardiovascular and cerebrovascular diseases, which seriously threaten human life and health. Among them, nearly half of cardiovascular disease patients suffer from severe hypertension complications. Hypertension is thought to cause abnormal platelet activation and increases the risk of thrombosis, but the related mechanism is still vague. Objectives This study hypothesized that the abnormal hemodynamics of blood under hypertension might affect platelet function and accelerate thrombosis by activating mechanoreceptor Piezo1. Methods To assess the activation effect of hypertension on mechanoreceptor Piezo1, we injected Piezo1 agonist Yoda1 and antagonist GsMTx‐4 through the tail vein, then examined the platelet activation status and thrombosis. Results Our results displayed that antagonist GsMTx‐4 effectively inhibited calcium influx caused by hypertension and agonist Yoda1. Antithrombotic studies proved that the inhibition of Piezo1 effectively inhibited arterial thrombosis and reduced the infarct size of stroke in hypertensive mice. Conclusions Our study explains the activation of mechanoreceptor Piezo1 under hypertension is the key to abnormal platelet activation and thrombosis while providing novel platelet intervention strategies to prevent thrombosis.

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“…5D, CA did not induce apoptosis in bladder cancer cells, suggesting that CA could cause a non-apoptotic cell death mode. Although induction of apoptosis has long been the most common mechanism of anti-cancer agents [22], the discovery of various cell death modes in recent years enables a broader view for screening novel anti-cancer agents [23]. Here, we discovered that CA suppressed bladder cancer cell proliferation at low concentrations and induced nonapoptotic cell death at high concentrations.…”

Section: Corosolic Acid At High Concentration Induced Non-apoptotic Cell Death In Bladder Cancer Cellsmentioning

confidence: 91%

Transcriptome and Proteome Analysis Reveals Corosolic Acid Inhibiting Bladder Cancer via Targeting Cell Cycle and Inducing Mitophagy in Vitro and in Vivo

Cui

et al. 2021

Preprint

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Background Existing chemotherapy and radiotherapy methods have drawbacks such as high toxicity, high side effects, poor efficacy, and chemoresistance. Therefore, there is an urgent need to develop new anti-cancer drugs with low toxicity and high efficiency for cancer therapy and the prevention of recurrence. Corosolic acid (CA) is a medicine and food homologue and has many biological activities of health care. However, the anti-tumor effects and mechanism of CA in bladder cancer remain unexplored. Methods To study the anticancer effect of CA on bladder cancer cells, CCK8, EdU, high-content living cell imaging experiments were performed. And the mice model was used to verify the anticancer effect and toxicity for mice. To investigate the molecular mechanism of CA inhibition on bladder cancer cells, transcriptomics and proteomics were employed. To further verify the pharmacological mechanism, flow cytometry, RT-qPCR, western blotting and immunofluorescence staining experiments were performed, and the CA targeting molecules were analyzed in combination with our experimental and public clinical data. Results We found that CA inhibited bladder cancer cell proliferation in a concentration- and time-dependent manner. Xenograft experiments showed that CA inhibited the growth of subcutaneous tumors, and had no toxicity in mice. Integration of omics analysis revealed that low concentrations of CA inhibited bladder cancer cells proliferation via attenuating DNA synthesis by downregulating TOP2A and LIG1, and via diminishing mitosis by downregulating CCNA2, CCNB1, CDC20, and RRM2. High concentrations of CA induced cell death not through the apoptotic pathway but through triggering mitophagy pathway via upregulating SQSTM1/P62, NBR1, and UBB. Conclusions CA, a natural compound homologous to medicine and food, inhibits the mitosis of bladder cancer cells at low concentrations, and kills bladder cancer cells by inducing mitophagy at high concentrations. This study provides a comprehensive understanding of the pharmacological mechanism of CA inhibition in bladder cancer for the first time, which is helpful for the development of new anti-tumor drugs based on CA.

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Apoptosis: A target for anticancer therapy with novel cyanopyridines

Cited by 39 publications

References 43 publications

Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity

Novel azo pyridone dyes based on dihydropyrimidinone skeleton: Synthesis, DFT study and anticancer activity

Piezo1 initiates platelet hyperreactivity and accelerates thrombosis in hypertension

Transcriptome and Proteome Analysis Reveals Corosolic Acid Inhibiting Bladder Cancer via Targeting Cell Cycle and Inducing Mitophagy in Vitro and in Vivo

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