Malignant diseases are responsible for the death of about one fifth of the population. The target of much research has been on the discovery of natural and synthetic compounds that can be used in the prevention and/or treatment of cancer. Many plants and animal extracts have shown various biological activities like immunopotentiating and antitumour activities. Honey bee propolis and its components (caffeic acid, caffeic acid phenethyl ester, artepilin C, quercetin, naringenin, resveratrol, galangin, genistein and other) are of the most promising as antitumour agent. [1][2][3][4][5][6][7][8] Propolis (bee glue) is the generic name for the resinous substance collected by honey bees from various plant sources and used by bees to seal holes in their honeycombs, smooth out the internal walls, and protect the entrance against intruders.1) It is rich in biochemical constituents, including mostly a mixture of polyphenols, flavonoid aglycones, phenolic acid and their esters, and phenolic aldehydes and ketones, terpenes, sterols, vitamins, amino acids, etc.2) Healing properties of propolis are known in folk medicine from antiquity. Recently, the interest for propolis as a harmless medicine is increasing. There have been many attempts to validate biological effects of propolis and elucidate its composition. [3][4][5][6][7][8] It was shown that propolis and its constituents have strong antimicrobial effect, acting on viruses, 9-11) bacteria, [12][13][14] and fungi. 15,16) It was also demonstrated that propolis and some of its active substances have a pronounced cytostatic, anticarcinogenic and antitumour effect both in "in vitro" and "in vivo" tumor models. [6][7][8][17][18][19][20][21][22] Immunomodulatory effects of propolis has also been recorded. [23][24][25][26] It has been suggested that the therapeutic activities of propolis depend mainly on the presence of flavonoids.28) Flavonoids have also been reported to induce the immune system, 29,30) and to act as strong oxygen radical scavengers. Dietary intake of antioxidant has been associated with a diminished risk of cancer at various anatomical sites. 31) This led us to compare how the routes (oral and/or systemic) of administration of different polyphenolic compounds deriving from propolis and of propolis itself influence on Ehrlich ascites tumor growth. Thus, we analyzed not only tumor growth but also parameters of immunomodulatory response of animals inoculated with test compounds, determining the effect of them on polymorphonuclear (PMN) and mononuclear (MN) cells, mainly macrophages.
MATERIALS AND METHODSWater-Soluble Derivative of Propolis (WSDP) Treatment A water-soluble derivative of propolis (WSDP) was prepared by the method described elsewhere. 32) Briefly, Croatian propolis from beehives kept at the outskirts of Zagreb, Croatia or Brazilian propolis (CONAP, Belo Horizonte, Minas Gerais, Brazil) was extracted with 96% ethanol, which was filtered and evaporated to dryness in vacuum evaporator. The resultant resinous product was added to a stirred solution of 8%...