Synergystic Antitumor Effect of Polyphenolic Components of Water Soluble Derivative of Propolis against Ehrlich Ascites Tumour

Abstract

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%...

Angiogenesis inhibition by green propolis and the angiogenic effect of L-lysine on bladder cancer in rats

“…Researchers have reported anti-infectious 3 , antiinflammatory 4 , immunomodulatory 5,6 , antitumor 7 , antioxidant [8][9][10] and antimetastatic 5 effects of WSDP. The discovery of the anticarcinogenic effects of propolis encouraged efforts to identify, isolate and synthesize constituents of propolis and to study their effects and mechanisms of action, including artepillin C 11 , caffeic acid 12 , caffeic acid phenethyl ester 13 , and in the present study, we used an in vivo model to evaluate the effect of intragastric administration of green propolis (in the form of WSDP) on angiogenesis in BBN-induced rat bladder cancer.…”

Efeito do tratamento com própolis de Scaptotrigona aff. postica sobre o desenvolvimento do tumor de Ehrlich em camundongos

“…O processo de carcinogênese apresenta vários estágios incluindo a iniciação, a promoção e a progressão do tumor (Almeida et al, 2005). Assim, o alvo de muitas pesquisas tem sido a descoberta de compostos naturais ou sintéticos que possam prevenir, retardar ou reverter o processo de carcinogênese (Orsolic et al, 2005a;b).…”

“…A partir de trabalhos publicados principalmente nas décadas de 80 e 90, a própolis de Apis mellifera L. vem recebendo especial atenção por suas várias propriedades biológicas, entre elas: antimicrobiana (Santos et al, 2002), antifúngica (Murad et al, 2002), antioxidante (Ahn et al, 2004), antitumoral (Orsolic et al, 2005a;b;Padmavathi et al, 2006), antiinflamatória, anestésica, cicatrizante (Reis et al, 2000).…”

“…Quercetina e galangina são flavonóides que têm sido identificados como promissores agentes antitumorais (Orsolic et al, 2005a;b). Compostos derivados do ácido cinâmico, como a artepilina C, encontrados nesta própolis, apresentam alta toxicidade para células tumorais (Matsuno et al, 1997;Salatino et al, 2005) e o isolamento de diterpenos tem demonstrado atividade anti-tumoral (Salatino et al, 2005).…”

Potential chemoprotective effects of green propolis, L-lysine and celecoxib on bone marrow cells and peripheral blood lymphocytes of Wistar rats subjected to bladder chemical carcinogenesis

“…Propolis is a resin produced by bees that has various antineoplasic 2 , antiinflammatory 3 , immunomodulatory 4 , antibacterial 5 and antiangiogenesis properties 6,7 . L-lysine is an essential amino acid and has been utilized in the extraction of propolis since the patented proposal of Nicolov et al 8 up to recent publications 2,3,7,9 . The objective of this work was to study the genotoxicity of green propolis and L-lysine on the bone marrow of rats subjected to chemical carcinogenesis of the bladder.…”