Cat's claw oxindole alkaloid isomerization induced by cell incubation and cytotoxic activity against T24 and RT4 human bladder cancer cell lines

Planta Med. 2013 Oct;79(15):1413-20. doi: 10.1055/s-0033-1350742. Epub 2013 Aug 23.


The antitumor activity of Uncaria tomentosa, a native vine from the Amazonian rainforest, has been ascribed to pentacyclic oxindole alkaloids occurring in its bark. Former studies have shown that this activity, as well as its intensity, depends on whether cat's claw alkaloids occur as original compounds or isomerized derivatives. This work addresses this aspect, using T24 and RT4 human bladder cancer cell lines for that purpose. Bark samples were extracted by dynamic maceration, prepurified with cross-linked polyvinylpyrrolidone and properly fractioned by an ion exchange process to obtain an oxindole alkaloid purified fraction. Alkaloid isomerization was induced by heating it under reflux at 85 °C. Samples collected after 5, 15, and 45 min of heating were analyzed by HPLC-PDA, freeze-dried at once, and separately assayed using the non-isomerized purified fraction for comparison purposes. The latter showed significant and dose-dependent cytotoxic activity against both T24 and RT4 cancer cell lines (IC50: 164.13 and 137.23 µg/mL, respectively). However, results for both cell lines were equivalent to those observed for isomerized samples (p > 0.05). The alkaloid isomerization induced by the incubation conditions (buffered medium pH 7.4 and temperature 37 °C) helps to explain the similar results obtained from non-isomerized and isomerized samples. Mitraphylline, speciophylline, uncarine F, and, to a lesser degree, pteropodine were more susceptible to isomerization under the incubation conditions. Thus, the alkaloid profile of all fractions and their cytotoxic activities against T24 and RT4 human bladder cancer cell lines are determined to a large extent by the incubation conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Cat's Claw / chemistry*
  • Cell Line, Tumor
  • Hot Temperature
  • Humans
  • Indole Alkaloids / chemistry*
  • Indole Alkaloids / isolation & purification
  • Indole Alkaloids / therapeutic use
  • Indoles / chemistry*
  • Indoles / isolation & purification
  • Indoles / therapeutic use
  • Isomerism
  • Oxindoles
  • Phytotherapy*
  • Plant Bark
  • Plant Extracts / chemistry*
  • Plant Extracts / therapeutic use
  • Urinary Bladder Neoplasms / drug therapy*


  • Antineoplastic Agents, Phytogenic
  • Indole Alkaloids
  • Indoles
  • Oxindoles
  • Plant Extracts
  • 2-oxindole