Uncaria tomentosa exerts extensive anti-neoplastic effects against the Walker-256 tumour by modulating oxidative stress and not by alkaloid activity

PLoS One. 2013;8(2):e54618. doi: 10.1371/journal.pone.0054618. Epub 2013 Feb 7.


This study aimed to compare the anti-neoplastic effects of an Uncaria tomentosa (UT) brute hydroethanolic (BHE) extract with those of two fractions derived from it. These fractions are choroformic (CHCl3) and n-butanolic (BuOH), rich in pentacyclic oxindole alkaloids (POA) and antioxidant substances, respectively. The cancer model was the subcutaneous inoculation of Walker-256 tumour cells in the pelvic limb of male Wistar rat. Subsequently to the inoculation, gavage with BHE extract (50 mg.kg(-1)) or its fractions (as per the yield of the fractioning process) or vehicle (Control) was performed during 14 days. Baseline values, corresponding to individuals without tumour or treatment with UT, were also included. After treatment, tumour volume and mass, plasma biochemistry, oxidative stress in liver and tumour, TNF-α level in liver and tumour homogenates, and survival rates were analysed. Both the BHE extract and its BuOH fraction successfully reduced tumour weight and volume, and modulated anti-oxidant systems. The hepatic TNF-α level indicated a greater effect from the BHE extract as compared to its BuOH fraction. Importantly, both the BHE extract and its BuOH fraction increased the survival time of the tumour-bearing animals. Inversely, the CHCl3 fraction was ineffective. These data represent an in vivo demonstration of the importance of the modulation of oxidative stress as part of the anti-neoplastic activity of UT, as well as constitute evidence of the lack of activity of isolated POAs in the primary tumour of this tumour lineage. These effects are possibly resulting from a synergic combination of substances, most of them with antioxidant properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Alkaloids / pharmacology
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Aspartate Aminotransferases / blood
  • Blotting, Western
  • Carcinoma 256, Walker / metabolism
  • Carcinoma 256, Walker / pathology*
  • Cat's Claw / chemistry*
  • Catalase / metabolism
  • Chromatography, High Pressure Liquid
  • Magnetic Resonance Spectroscopy
  • Oxidative Stress / drug effects*
  • Plant Extracts / pharmacology*
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Catalase
  • Superoxide Dismutase
  • Aspartate Aminotransferases
  • Alanine Transaminase

Grant support

The authors would like to express their gratitude to Dr. José Luis Aguilar, from the Cayetano Heredia Peruvian University, Lima, Peru; Dr. Armando Rivero, from the National University of San Marcos, Lima, Peru; and Peruvian Heritage, S.A.C., for their generous contribution of all botanic material employed in this work. Also, all our appreciation goes to Prof. Dr. Luiz Cláudio Fernandes, Federal University of Paraná, for his kindness in providing us with the Walker-256 tumour cells. Finally, many thankful regards go to Jorgete Constantin, Aparecida Pinto Munhos Hermoso and Renato Polimeni Constantin, from the University of Maringá, Paraná, Brazil, for their invaluable help during some experimental procedures. The authors acknowledge REUNI/CAPES for the Master degree fellowship supported to the first author. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.