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Cytotoxic Effect of Natural trans-Resveratrol Obtained from Elicited Vitis vinifera Cell Cultures on Three Cancer Cell Lines

Abstract

trans-Resveratrol (trans-R) has been reported to be a potential cancer chemopreventive agent. Although its cytotoxic activity against different cancer cell lines has been tested, its effect on human acute leukemia cell lines has scarcely been investigated, and only a few in vitro studies were performed using human breast epithelial cell lines. Due to its potential value for human health, demand for trans-R has rapidly increased, and new biotechnological strategies to obtain it from natural edible sources have been developed. Thus, grapevine cell cultures represent a reliable system of trans-R production since they biosynthesize trans-R constitutively or in response to elicitation. In addition, there are no studies deepen on the inhibitory effect of trans-R, produced by elicited grapevine cell cultures, on growth of human tumor cell lines. In this work, the effect of trans-R extracted from the culture medium, after elicitation of grapevine cell cultures, was tested on two human acute lymphocytic and monocytic leukemia cell lines, and one human breast cancer cell line. The effect of trans-R on cell proliferation was not only dose- and time-dependent but also cell type-dependent, as seen from the different degrees of susceptibility of cancer cell lines tested. As regards the effect of trans-R on cell cycle distribution, low trans-R concentrations increased cells in the S phase whereas a high trans-R concentration increased G0/G1 phase in all cell lines. Perturbation of the cell cycle at low trans-R concentrations did not correlate with the induction of cell death, whereas a high trans-R concentration, cell proliferation decreased as a result of increasing apoptosis in the three cell lines. In leukemia cells, trans-R up-regulated the expression of caspase-3 while trans-R-induced apoptosis in breast cells occur through a caspase-3-independent mechanism mediated by a down-regulation of Bcl-2.

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Abbreviations

CDs:

Cyclodextrins

IC50 :

Median inhibitory concentration

trans-R:

trans-Resveratrol

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Acknowledgments

F. Fernández-Pérez and L. Almagro have grants from the MICINN. This study was supported by the Fundación Séneca, Agencia de Ciencia y Tecnología de la Región de Murcia en el marco de II PCTRM 2007-10 (08799/PI/08) and by MICINN-FEDER (BIO2008-2941 and BIO2011-29856-C02-02).

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Correspondence to Maria A. Pedreño.

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Francisco Fernández-Pérez, Sarai Belchí-Navarro and Lorena Almagro contributed equally to this work.

This work is dedicated in memoriam of Prof. Alfonso Ros-Barceló our mentor and friend.

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Fernández-Pérez, F., Belchí-Navarro, S., Almagro, L. et al. Cytotoxic Effect of Natural trans-Resveratrol Obtained from Elicited Vitis vinifera Cell Cultures on Three Cancer Cell Lines. Plant Foods Hum Nutr 67, 422–429 (2012). https://doi.org/10.1007/s11130-012-0327-8

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Keywords

  • Antitumor
  • Grapevine cell cultures
  • Elicitation
  • trans-Resveratrol
  • Human cancer cell lines