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Resveratrol-induced potentiation of the antitumor effects of oxaliplatin is accompanied by an altered cytokine profile of human monocyte-derived macrophages

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Abstract

The objective of this study was to investigate, whether the naturally occurring polyphenol resveratrol (Res) enhances the anti-tumor activities of the chemotherapeutic agent oxaliplatin (Ox) in a cell culture model of colorectal cancer, also with regard to a possible inflammatory response and cytotoxic side-effects. Res and Ox in combination synergistically inhibit cell growth of Caco-2 cells, which seems to be due to the induction of different modes of cell death and further leads to an altered cytokine profile of cocultured macrophages. Moreover, combinatorial treatment does not affect non-transformed cells as severe cytotoxicity is not detected in human foreskin fibroblasts and platelets.

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Abbreviations

BrdU:

Bromodeoxyuridine

CI:

Combination index

DMEM:

Dulbecco’s modified-Eagle’s medium

DMSO:

Dimethylsulfoxide

EDTA:

Ethylendiaminetetraacetic acid

FCS:

Fetal calf serum

FITC:

Fluorescein isothiocyanate

5-FU:

5-Fluorouracil

HFF:

Human foreskin fibroblasts

IAPs:

Inhibitor of apoptosis proteins

IC50 :

Half maximal inhibitory concentration

IL:

Interleukine

LDH:

Lactate dehydrogenase

Ox:

Oxaliplatin

PARP:

Poly[ADP-ribose] polymerase

PI:

Propidium iodide

Res:

Resveratrol

TAMs:

Tumor associated macrophages

TNF-α:

Tumor necrosis factor-α

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Acknowledgments

This work was supported by Graduate Scholarship Grants from the DFG to Bettina M. Kaminski and from the “Stiftung Polytechnische Gesellschaft Frankfurt am Main” to Maria-Christina Scherzberg. Bettina M. Kaminski was a member of the Frankfurt International Research Graduate School for Translational Biomedicine (FIRST), Frankfurt am Main. The authors thank Astrid Brüggerhoff for excellent technical assistance.

Conflict of interest

The authors have declared no conflict of interest.

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Authors and Affiliations

  1. Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany

    Bettina M. Kaminski, Maria-Christina Scherzberg, Bianca Gilbert, Dieter Steinhilber, Jürgen Stein & Sandra Ulrich-Rückert

  2. Department of Internal Medicine, Sachsenhausen Hospital, Frankfurt am Main, Germany

    Jürgen Stein

  3. Institute of Biochemistry I/ZAFES, Goethe University, Frankfurt am Main, Germany

    Andreas Weigert, Stephanie Ley, Kerstin Brecht & Bernhard Brüne

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  1. Bettina M. Kaminski
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Correspondence to Sandra Ulrich-Rückert.

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Kaminski, B.M., Weigert, A., Scherzberg, MC. et al. Resveratrol-induced potentiation of the antitumor effects of oxaliplatin is accompanied by an altered cytokine profile of human monocyte-derived macrophages. Apoptosis 19, 1136–1147 (2014). https://doi.org/10.1007/s10495-014-0988-x

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