Ursolic acid-induced changes in tumor growth, O2 consumption, and tumor interstitial fluid pressure

Anticancer Res. Jul-Aug 2001;21(4A):2827-33.

Abstract

The anti-tumor effect of ursolic acid (UA) and UA-induced changes in tumor physiology in tumor-bearing mice were examined. MTT colorimetric assay, clonogenic assay, and growth-delay assay for the determination of tumoricidal effects of UA were evaluated. UA-induced apoptosis was measured by fluorescent microscopy, stained by propidium iodide. Oxygen consumption (QO2) after treatment with UA was measured using a Clark-type electrode chamber. Systemic toxicity in mice was assayed by LD50(30). We also measured UA-induced changes in several tumor physiological parameters. Inhibitory effect of UA on various tumor cell lines was observed using MTT and clonogenic assays in vitro. UA-induced apoptosis significantly increased in a dose-dependent manner. Cellular QO2 values were significantly reduced by UA. In animal studies, UA significantly reduced tumor interstitial fluid pressure (TIFP) to approximately 40% of the control values at 2-3 days post-treatment (P<0.05). An i.p. administration of 100 mg/kg of UA significantly (P<0.01) inhibited tumor growth of FSaII. In conclusion, UA showed anti-tumor effect on various tumor cells in vitro as well as a moderate retardation of growth in two tumor models in vivo. We gained some insight regarding the pathophysiological benefits of UA (i.e., reduction in TIFP) as a cancer therapeutic agent. Consequently, these observations can be used for further study of UA or to facilitate clinical applications of UA for treating cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Division / drug effects
  • Dose-Response Relationship, Drug
  • Extracellular Space / drug effects
  • Extracellular Space / physiology
  • Female
  • Humans
  • Lethal Dose 50
  • Mice
  • Mice, Inbred C3H
  • Neoplasms, Experimental / blood supply
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Oxygen Consumption / drug effects*
  • Triterpenes / pharmacology*
  • Triterpenes / toxicity
  • Tumor Cells, Cultured / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Triterpenes
  • ursolic acid