Evidence of vanillin binding to CAMKIV explains the anti-cancer mechanism in human hepatic carcinoma and neuroblastoma cells

Naz, Huma; Tarique, Mohd; Khan, Parvez; Luqman, Suaib; Ahamad, Shahzaib; Islam, Asimul; Ahmad, Faizan; Hassan, Md. Imtaiyaz

doi:10.1007/s11010-017-3111-0

Cited by 66 publications

(47 citation statements)

References 59 publications

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“…Study also demonstrated that inhibition of neuronal apoptosis was associated with the downregulation of CAMK4 29 . A latest finding also indicated that CAMK4 could inhibit the proliferation of HepG2 and neuroblastoma cells (SH-SY5Y) by combining with Vanillin to increase the viability of CAMK4 30 . Lin 31 suggested that CaMKIV was an important regulator of liver cancer.…”

Section: Discussionmentioning

confidence: 96%

MiR-129-5p inhibits liver cancer growth by targeting calcium calmodulin-dependent protein kinase IV (CAMK4)

Zeng

et al. 2019

Cell Death Dis

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This study was designed to investigate the mechanism by which miR-129-5p affects the biological function of liver cancer cells. The expression levels of miR-129–5p in liver cancer tissues and cells were, respectively, determined. Crystal violet staining and flow cytometry were used to detect cell proliferation and apoptosis. Wound healing assay and transwell assay were performed to test cell migration and invasion. The target gene of miR-129–5p was analyzed and verified by bioinformatics analysis and luciferase reporter assay. Tumorigenicity assays in nude mice were used to test the antitumor ability of calcium calmodulin-dependent protein kinase IV (CAMK4). miR-129–5p was found to be underexpressed in hepatocellular cancer tissues and cells and also to inhibit liver cells proliferation, migration, and invasion and promote apoptosis. CAMK4 was a direct target for miR-129–5p and was lowly expressed in liver cancer tissues and cells. CAMK4 was also found to inhibit liver cells proliferation, migration and invasion, and promote apoptosis. CAMK4 might exert an antitumor effect by inhibiting the activation of mitogen-activated protein kinase (MAPK). MiR-129–5p was a tumor suppressor with low expression in liver cancer tissues and cells. CAMK4, which is a direct target gene of miR-129–5p, could inhibit tumor by inhibiting the activation of MAPK signaling pathway.

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Section: Discussionmentioning

confidence: 96%

MiR-129-5p inhibits liver cancer growth by targeting calcium calmodulin-dependent protein kinase IV (CAMK4)

Zeng

et al. 2019

Cell Death Dis

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“…In this respect, Srinual and coworkers have established that vanillin suppresses cancer stemness phenotypes in the human non-small cell lung cancer NCI-H460 cell line through the downregulation of CD133 and ALDH1A1 and the associated transcription factors, Oct4 and Nanog [ 61 ]. Furthermore, in human hepatocyte carcinoma and neuroblastoma models the antioxidant properties are strictly related to the vanillin-mediated antineoplastic efforts, because it significantly reduces the mitochondrial membrane depolarization and ROS production, leading to apoptosis induction [ 62 ]. Taking into consideration this evidence and in light of the cardioprotective results shown in the present study, it is conceivable to develop a therapeutic regimen in which vanillin is used either as adjuvant chemotherapy agent or just heart injury defending compound.…”

Section: Discussionmentioning

confidence: 99%

Vanillin Prevents Doxorubicin-Induced Apoptosis and Oxidative Stress in Rat H9c2 Cardiomyocytes

et al. 2020

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Doxorubicin (doxo) is an effective anticancer compound in several tumor types. However, as a consequence of oxidative stress induction and ROS overproduction, its high cardiotoxicity demands urgent attention. Vanillin possesses antioxidant, antiproliferative, antidepressant and anti-glycating properties. Therefore, we investigated the potential vanillin protective effects against doxo-induced cardiotoxicity in H9c2 cells. Using multiparametric approach, we demonstrated that vanillin restored both cell viability and damage in response to doxo exposure. Contextually, vanillin decreased sub-G1 appearance and caspase-3 and PARP1 activation, reducing the doxo-related apoptosis induction. From a mechanistic point of view, vanillin hindered doxo-induced ROS accumulation and impaired the ERK phosphorylation. Notably, besides the cardioprotective effects, vanillin did not counteract the doxo effectiveness in osteosarcoma cells. Taken together, our results suggest that vanillin ameliorates doxo-induced toxicity in H9c2 cells, opening new avenues for developing alternative therapeutic approaches to prevent the anthracycline-related cardiotoxicity and to improve the long-term outcome of antineoplastic treatment.

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“…However, there are representatives of nonflavonoids also that show inhibitory effects for human kinases, including resveratrol, caffeic acid, and gallic acid [ 29 , 30 ]. Our previous studies demonstrated the binding and inhibition of CaMKIV by various natural compounds including hesperidin, β -carotene, and vanillin [ 31 – 33 ]. These compounds also showed the antiproliferative effect in breast (MCF-7), liver (HuH7 and HepG2), and neuroblastoma cancer cells (SH-SY5Y).…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential Inhibitors of Calcium/Calmodulin-Dependent Protein Kinase IV from Bioactive Phytoconstituents

Gupta

Khan

Fakhar

et al. 2020

Oxidative Medicine and Cellular Longevity

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Calcium/calmodulin-dependent protein kinase IV (CaMKIV) is an upstream regulator of CaMKK-CaMKIV signaling cascade that activates various transcription factors, thereby regulating several cellular activities including, neuronal communication and immune response. Owing to the abnormal expression in cancer and neurodegenerative diseases, the CaMKIV has been considered a potential drug target. In the present study, we checked the binding affinity of plant-derived natural compounds viz., quercetin, ellagic acid (EA), simvastatin, capsaicin, ursolic acid, DL-α-tocopherol acetate, and limonin towards CaMKIV. Molecular docking and fluorescence binding studies showed that EA and quercetin bind to the CaMKIV with a considerable affinity in comparison to other compounds. Enzyme inhibition assay revealed that both EA and quercetin inhibit CaMKIV activity with their IC50 values in the micromolar range. To get atomistic insights into the mode of interactions, inhibition mechanism, and the stability of the CaMKIV-ligand complex, a 100 ns MD simulation analysis was performed. Both EA and quercetin bind to the catalytically important residues of active site pocket of CaMKIV forming enough stabilizing interactions presumably inhibiting enzyme activity. Moreover, no significant structural change in the CaMKIV was observed upon binding of EA and quercetin. In conclusion, this study illustrates the application of phytoconstituents in the development of therapeutic molecules targeting CaMKIV having implications in cancer and neurodegenerative diseases after in vivo validation.

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Evidence of vanillin binding to CAMKIV explains the anti-cancer mechanism in human hepatic carcinoma and neuroblastoma cells

Cited by 66 publications

References 59 publications

MiR-129-5p inhibits liver cancer growth by targeting calcium calmodulin-dependent protein kinase IV (CAMK4)

MiR-129-5p inhibits liver cancer growth by targeting calcium calmodulin-dependent protein kinase IV (CAMK4)

Vanillin Prevents Doxorubicin-Induced Apoptosis and Oxidative Stress in Rat H9c2 Cardiomyocytes

Identification of Potential Inhibitors of Calcium/Calmodulin-Dependent Protein Kinase IV from Bioactive Phytoconstituents

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