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Gallic Acid, an Active Constituent of Grape Seed Extract, Exhibits Anti-proliferative, Pro-apoptotic and Anti-tumorigenic Effects Against Prostate Carcinoma Xenograft Growth in Nude Mice

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Abstract

Purpose

Gallic acid, a natural agent present in a wide-range of fruits and vegetables, has been of potential interest as an anti-cancer agent; herein, we evaluated its efficacy in androgen-independent DU145 and androgen-dependent-22Rv1 human prostate cancer (PCa) cells.

Materials and Methods

Cell viability was determined by MTT and apoptosis by Annexin V-PI assays. In vivo anti-cancer efficacy was assessed by DU145 and 22Rv1 xenograft growth in nude mice given normal drinking water or one supplemented with 0.3% or 1% (w/v) gallic acid. PCNA, TUNEL and CD31 immunostaining was performed in tumor tissues for in vivo anti-proliferative, apoptotic and anti-angiogenic effects of gallic acid.

Results

Gallic acid decreased cell viability in a dose-dependent manner in both DU145 and 22Rv1 cells largely via apoptosis induction. In tumor studies, gallic acid feeding inhibited the growth of DU145 and 22Rv1 PCa xenografts in nude mice. Immunohistochemical analysis revealed significant inhibition of tumor cell proliferation, induction of apoptosis, and reduction of microvessel density in tumor xenografts from gallic acid-fed mice as compared to controls in both DU145 and 22Rv1 models.

Conclusion

Taken together, our findings show the anti-PCa efficacy of gallic acid and provide a rationale for additional studies with this naturally-occurring agent for its efficacy against PCa.

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Abbreviations

DAB:

3,3′-diaminobenzidine

MTT:

Thiazolyl Blue Tetrazolium Bromide

PCNA:

Proliferating cell nuclear antigen

TUNEL:

Terminal deoxynucleotidyl transferase-mediated UTP nick end labeling

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ACKNOWLEDGEMENTS

This study was supported by the National Cancer Institute, NIH RO1 grant CA091883.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, C238- P15, Research 2, Room 3122, 12700 19th Ave., Aurora, Colorado, 80045, USA

    Manjinder Kaur, Balaiya Velmurugan, Subapriya Rajamanickam, Rajesh Agarwal & Chapla Agarwal

  2. University of Colorado Cancer Center, University of Colorado Denver, Aurora, Colorado, 80045, USA

    Rajesh Agarwal & Chapla Agarwal

Authors
  1. Manjinder Kaur
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  2. Balaiya Velmurugan
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  3. Subapriya Rajamanickam
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  4. Rajesh Agarwal
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  5. Chapla Agarwal
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Corresponding author

Correspondence to Chapla Agarwal.

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Kaur, M., Velmurugan, B., Rajamanickam, S. et al. Gallic Acid, an Active Constituent of Grape Seed Extract, Exhibits Anti-proliferative, Pro-apoptotic and Anti-tumorigenic Effects Against Prostate Carcinoma Xenograft Growth in Nude Mice. Pharm Res 26, 2133–2140 (2009). https://doi.org/10.1007/s11095-009-9926-y

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  • DOI: https://doi.org/10.1007/s11095-009-9926-y

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