Molecular and Cellular Biochemistry

, Volume 438, Issue 1–2, pp 35–45 | Cite as

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

  • Huma Naz
  • Mohd Tarique
  • Parvez Khan
  • Suaib Luqman
  • Shahzaib Ahamad
  • Asimul Islam
  • Faizan Ahmad
  • Md. Imtaiyaz Hassan
Article
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Accepted:

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.

Keywords

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

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).

Compilance with ethical standards

Conflict of interest

The authors have no conflicts of interest with the current work or its publication.

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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Centre for Interdisciplinary Research in Basic Sciences,Jamia Millia IslamiaNew DelhiIndia
  2. 2.Department of BiochemistryAll India Institute of Medical SciencesNew DelhiIndia
  3. 3.CSIR-Central Institute of Medicinal and Aromatic PlantsLucknowIndia
  4. 4.Department of BiotechnologyCollege of Engineering & Technology, IFTM UniversityMoradabadIndia

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