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

Abstract

Human calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a member of Ser/Thr kinase family, and is associated with different types of cancer and neurodegenerative diseases. Vanillin is a natural compound, a primary component of the extract of the vanilla bean which possesses varieties of pharmacological features including anti-oxidant, anti-inflammatory, anti-bacterial and anti-tumor. Here, we have investigated the binding mechanism and affinity of vanillin to the CAMKIV which is being considered as a potential drug target for cancer and neurodegenerative diseases. We found that vanillin binds strongly to the active site cavity of CAMKIV and stabilized by a large number of non-covalent interactions. We explored the utility of vanillin as anti-cancer agent and found that it inhibits the proliferation of human hepatocyte carcinoma (HepG2) and neuroblastoma (SH-SY5Y) cells in a dose-dependent manner. Furthermore, vanillin treatment resulted into the significant reduction in the mitochondrial membrane depolarization and ROS production that eventually leads to apoptosis in HepG2 and SH-SY5Y cancer cells. These findings may offer a novel therapeutic approach by targeting the CAMKIV using natural product and its derivative with a minimal side effect.

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Acknowledgements

This work is supported by the Indian Council of Medical Research (Grant No. BIC/12(01)/2015). HN and PK thank to the ICMR for the fellowship. We sincerely acknowledge Harvard University-plasmid providing facility for providing the CAMK4 gene. Authors thank to the Department of Science and Technology, Government of India for the FIST support (No. SR/FST/LSI-541/2012).

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Correspondence to Md. Imtaiyaz Hassan.

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Naz, H., Tarique, M., Khan, P. et al. Evidence of vanillin binding to CAMKIV explains the anti-cancer mechanism in human hepatic carcinoma and neuroblastoma cells. Mol Cell Biochem 438, 35–45 (2018). https://doi.org/10.1007/s11010-017-3111-0

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  • DOI: https://doi.org/10.1007/s11010-017-3111-0

Keywords

  • Calcium/calmodulin-dependent protein kinase IV
  • Vanillin
  • Apoptosis
  • ROS
  • Human hepatocyte carcinoma and neuroblastoma cells