Planta Med 2006; 72(1): 20-27
DOI: 10.1055/s-2005-873167
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Direct and Indirect Mechanism(s) of Antitumour Activity of Propolis and its Polyphenolic Compounds

Nada Oršolić1 , Ana Brbot Šaranović2 , Ivan Bašić1
  • 1Department of Animal Physiology, Faculty of Science, University of Zagreb, Zagreb, Croatia
  • 2Department of Chemistry, Veterinary Faculty, University of Zagreb, Zagreb, Croatia
Further Information

Publication History

Received: December 22, 2004

Accepted: June 20, 2005

Publication Date:
10 November 2005 (online)


The immunomodulatory actions of a water-soluble derivative of propolis (WSDP) and two components of propolis, caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) were investigated. Oral administration (50 mg/kg) of WSDP, CA, and CAPE enhanced the weight and cellularity of the spleen (p < 0.05, p < 0.01) of treated mice. The response of spleen cells to polyclonal mitogens (PHA, Con A, PWM) was also increased in mice treated with WSDP as compared to control (p < 0.01); in contrast, the response of spleen cells of mice treated with CA were significantly suppressed (p < 0.001). The colony forming ability of HeLa cells plated on monolayers of macrophages was completely inhibited by peritoneal macrophages from mice receiving either WSDP, CAPE, or CA. Macrophages from treated mice also inhibited [3 H]TdR incorporation into HeLa cells in vitro. Testing for the possible presence of NO in the supernatants of 24 hours cultured macrophages activated with either compound revealed that the toxicity of these cells to HeLa cells was in part due to the production of NO. Tumour growth was suppressed by WSDP and its polyphenolic compounds given orally to mice. Local presence of CA, and CAPE in the tissue, caused a significant delay of tumour formation. Based on these results, we postulate that the antitumour activity of the test compounds includes pronounced immunomodulatory activity mainly due to the augmentation of non-specific antitumour resistance in mice via macrophage activation and the production of soluble factors by those cells which may interfere with either cells of the immune system or directly by tumour cells.


WSDP:water-soluble derivative of propolis

CA:caffeic acid

CAPE:caffeic acid phenethyl ester

NO:nitric oxide

NOS:nitric oxide syntase

[3 H]-TdR:[3 H]-thymidine


Nada Oršolić

Department of Animal Physiology

Faculty of Science

University of Zagreb

10000 Zagreb

Rooseveltov trg 6


Phone: +385-1-4826-266

Fax: +385-1-4826-269/280/313

Email: [email protected]