Valproic acid reduces tumor cell survival and proliferation with inhibitors of downstream molecules of epidermal growth factor receptor pathway

Bhuvanesh Sukhlal Kalal, Vinitha Ramanath Pai, Dinesh Upadhya

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)11-16
Number of pages6
JournalJournal of Pharmacology and Pharmacotherapeutics
Volume9
Issue number1
DOIs
Publication statusPublished - 01-01-2018

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Valproic Acid
Epidermal Growth Factor Receptor
Cell Survival
Cell Proliferation
Phosphatidylinositol 3-Kinases
Phosphotransferases
Neoplasms
Deoxyuridine
Growth
Caspases
Cell Death

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

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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.",
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Valproic acid reduces tumor cell survival and proliferation with inhibitors of downstream molecules of epidermal growth factor receptor pathway. / Kalal, Bhuvanesh Sukhlal; Pai, Vinitha Ramanath; Upadhya, Dinesh.

In: Journal of Pharmacology and Pharmacotherapeutics, Vol. 9, No. 1, 01.01.2018, p. 11-16.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Pai, Vinitha Ramanath

AU - Upadhya, Dinesh

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AB - 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.

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