Simvastatin Strongly Augments Proapoptotic, Anti-inflammatory and Cytotoxic Activity of Oxicam Derivatives in Doxorubicin-resistant Colon Cancer Cells.

Abstract

BACKGROUND:

Incidence of cancer is still increasing. Chemotherapy is often unsuccessful; moreover, anticancer drugs cause serious side-effects. It is necessary to develop effective agents for combination therapies that would increase antitumor effects of treatment and reduce its side-effects.

MATERIALS AND METHODS:

Anticancer activity of oxicam derivatives (PR17 and PR18) alone and in combination with simvastatin on doxorubicin-resistant colon cancer cells was studied. Apoptosis was investigated via caspase-3 activation assay as well as via western blot analysis of expression of apoptotic components, B-cell lymphoma 2 protein (BCL2) and BCL2-associated X protein (BAX). Expression and activity of cyclo-oxygenase-2 (COX2) was also assessed.

RESULTS:

Oxicam derivatives induced apoptosis through a caspase-3-dependent pathway, up-regulated BAX expression, and down-regulated BCL2 expression. Additionally, oxicam derivatives reduced expression and activity of COX2. Effect of oxicam derivatives on these processes was strongly potentiated by simvastatin.

CONCLUSION:

Oxicam derivatives at low concentrations effectively inhibit growth of cancer cells after co-administration with simvastatin.

• Authors: Kamila Środa-Pomianek, Krystyna Michalak, Anna Palko-Łabuz, Anna Uryga, Berenika Szczęśniak-Sięga, Olga Wesołowska
• Journal: Anticancer research (Anticancer Res) Vol. 39 Issue 2 Pg. 727-734 (Feb 2019) ISSN: 1791-7530 [Electronic] Greece
• PMID: 30711951 (Publication Type: Journal Article)
• Copyright: Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antineoplastic Agents
• BAX protein, human
• BCL2 protein, human
• Cyclic S-Oxides
• Proto-Oncogene Proteins c-bcl-2
• Thiazines
• bcl-2-Associated X Protein
• oxicam PR18
• Doxorubicin
• Simvastatin
• Cyclooxygenase 2
• PTGS2 protein, human
• CASP3 protein, human
• Caspase 3

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Cell Survival
• Colonic Neoplasms (pathology)
• Cyclic S-Oxides (chemistry, pharmacology)
• Cyclooxygenase 2 (metabolism)
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm
• Drug Synergism
• Enzyme Activation
• Humans
• Inhibitory Concentration 50
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Simvastatin (pharmacology)
• Thiazines (chemistry, pharmacology)
• Up-Regulation
• bcl-2-Associated X Protein (metabolism)