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Priming effect of aspirin for tumor cells to augment cytotoxic action of cisplatin against tumor cells: implication of altered constitution of tumor microenvironment, expression of cell cycle, apoptosis, and survival regulatory molecules

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Abstract

The present study was conducted to investigate if anti-inflammatory drug aspirin could alter the cytotoxic action of cisplatin on tumor cells. Using a transplantable T cell lymphoma in a murine model, we demonstrate that exposure to aspirin exerts a priming action on tumor cells, rendering them susceptible to induction of cell death by cisplatin with consequences on retardation of tumor progression. The priming action of aspirin on tumor cells was found to be dependent on an altered constitution of tumor microenvironment with respect to decline of acidosis and modulation in the expression of cell cycle and survival regulatory molecules like cyclin B1, cyclin D, bcl-2, bcl-xL, p53, and cytokines: IL-4, IL-10, IFN- γ & VEGF. The study also discusses possible mechanisms underlying augmentary action of aspirin on cisplatin-mediated tumor cells killing. This is the first report showing that pre-exposure of tumor cells to aspirin lowers the concentration of cisplatin to exert its cytotoxic action. The finding of this study will help in designing novel antitumor protocols with reduced dose of cisplatin.

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Abbreviations

Asp:

Aspirin

CP:

Cisplatin

DL:

Dalton’s lymphoma

DLAF:

DL ascitic fluid

IFN-γ:

Interferon-gamma

IL:

Interleukin

i.p.:

Intraperitoneal

HIF:

Hypoxia inducible factor

MTT:

[3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide]

NSAIDs:

Nonsteroidal anti-inflammatory drugs

PI:

Propidium iodide

SDS:

Sodium dodecyl sulfate

VEGF:

Vascular endothelial growth factor

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Acknowledgments

Financial support to School of Biotechnology from DBT, New Delhi is acknowledged. The authors express gratitude to UGC-New Delhi for senior research fellowship support to Anjani Kumar. We are grateful to Dr. S. D. Singh, Parul Pathology Laboratory, Varanasi, India, for his kind help in various assays. Aspirin was obtained as a kind gift from Alta Laboratory (Mumbai, India).

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Correspondence to Sukh Mahendra Singh.

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Kumar, A., Singh, S.M. Priming effect of aspirin for tumor cells to augment cytotoxic action of cisplatin against tumor cells: implication of altered constitution of tumor microenvironment, expression of cell cycle, apoptosis, and survival regulatory molecules. Mol Cell Biochem 371, 43–54 (2012). https://doi.org/10.1007/s11010-012-1421-9

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  • DOI: https://doi.org/10.1007/s11010-012-1421-9

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