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JPP · Lens · Valproic Acid Reduces Tumor Cell Survival and Proliferation with Inhibitors of Downstream Molecules of Epidermal Growth Factor Receptor Pathway

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Article · Volume 9, Issue 1 · pp. 11–6

Valproic Acid Reduces Tumor Cell Survival and Proliferation with Inhibitors of Downstream Molecules of Epidermal Growth Factor Receptor Pathway

Bhuvanesh Sukhlal Kalal1,2, Vinitha Ramanath Pai2, Dinesh Upadhya3

  1. 1Yenepoya Research Centre, Yenepoya University.
  2. 2Department of Biochemistry, Yenepoya Medical College, Yenepoya University, Mangalore.
  3. 3Department of Anatomy, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.

Abstract

Objectives: To evaluate the beneficial effect of treating tumor cells with valproic acid (VPA) in combination with inhibitors of various downstream molecules of epidermal growth factor receptor pathway for limiting tumor cell growth.Materials and Methods: Cytotoxic effect of VPA was tested with various combinations of inhibitors of PI3K‑AKT, ERK1/2, Jun N‑terminal kinases (JNK) as well as p38 kinases in A375 cells using methyl‑thiazol‑tetrazolium assay, clonogenic assay, and caspase assay. Antiproliferative effect of the combination was tested with ethynyl‑2′‑deoxyuridine incorporation assay.Results: Among the combinations tested, a combination of VPA with PI3K‑AKT inhibitor showed enhanced tumor cell death and reduced tumor cell proliferation compared to the combination of VPA with ERK1/2, JNK, and p38 inhibitors at lower doses.Conclusions: Combination of VPA with PI3K‑AKT inhibitor at lower concentration reduced tumor cell growth.

Keywords: Cancer; histone deacetylase inhibitors; Ly294002; valproic acid

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