Cell Growth Inhibitory Effect of Cinnamic Acid Derivatives from Propolis on Human Tumor Cell Lines

Abstract

A cell growth inhibitory effect of drupanin and baccharin, ingredients of propolis, was found in human cancer cell lines. These compounds induced apoptosis in the cells characterized by morphological and nucleosomal DNA fragmentation analysis. Their effects were less potent compared with that of artepillin C, which is a known anticancer compound from propolis. Importantly, HL60 cells were more sensitive to drupanin than were Con A-stimulated peripheral blood lymphocytes, whereas the potency of artepillin C was the opposite of that of drupanin.Key words propolis; drupanin; cell growth inhibition; apoptosis; human tumor cell Propolis is a sticky mixed substance that is collected from plant materials by honeybees.1) It has been considered that propolis is a protective wall against the enemies of bees. Propolis has been uesd as a folk medicine in Europe and Japan, and it is believed that propolis exerts a therapeutic or preventive effect in inflammation, heart disease, and even diabetes mellitus and cancer. Chemical analysis using GCmass spectrometry demonstrated that approximately 150 polyphenolic compounds including flavonoids and cinnamic acid derivatives are present in propolis.2) There have been several reports indicating various biological activities of propolis and its constituents, such as anticancer, 3,4) antioxidant, 5) antiinflammatory 6) and antibiotic 7) activities. Evaluation of the biological activities of ingredients in propolis and elucidation of the mechanisms of their functions provide substantial clues for the development of new drug candidates. In the course of phytochemical studies on biologically active compounds from propolis, we examined the anticancer activity of the ethanol extract fraction from propolis and found that two cinnamic acid derivatives showed growth inhibitory activity against human tumor cell lines. It has been reported that artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) from propolis exhibits antitumor activity by induction of apoptosis in human tumor cell lines in vitro. 8,9) In the present study, we demonstrated cell growth inhibition by drupanin and (E)-3-prenyl-4-(2,3-dihydrocinnamoyloxy) cinnamic acid, named baccharin by us, in human tumor cell lines and compared them with artepillin C.Brazilian propolis was extracted with 90% ethanol (EtOH) at room temperature to yield the extract. The EtOH extract was chromatographed over silica gel and the column (70 mm i.d.ϫ330 mm) was eluted stepwise with 2-70% CHCl 3 -methanol (MeOH). The 11 CHCl 3 -MeOH-eluted fractions were evaporated and then solubilized with 100% EtOH. The fractions were examined for cell growth inhibition and the fractions showing growth inhibitory effect against human tumor cell lines were further analyzed with HPLC (column: Shiseido AG120; gradient system-A solvent: 20% CH 3 CN/2% AcOH and B solvent: 100% CH 3 CN/2% AcOH; 20-100%; 0-60 min; flow rate: 1 ml/min; detection: UV 280 nm). After purification of the active compounds, their structures were determined by nuclear magnetic resonance ( 1 H-NMR) ana...

Perfis físico-químico e cromatográfico de amostras de própolis produzidas nas microrregiões de Franca (SP) e Passos (MG), Brasil

“…Geralmente, a presença desses componentes juntamente com fragmentos de B. dracunculifolia caracteriza a própolis denominada verde. Segundo Akao, et al (2003), atividades biológicas extremamente importantes, como por exemplo, atividade antitumoral de extratos hidroalcoólicos desse tipo de própolis podem ser atribuídas principalmente à presença destes três ácidos fenólicos. Assim, com base nesse conjunto de resultados pode-se sugerir que os extratos hidroalcoólicos de amostras de própolis destes dois locais poderiam ser utilizados para o consumo humano.…”

Análise de própolis

“…Este tipo de própolis vem se destacando por sua acentuada propriedade antimicrobiana [45], tendo o artepillin C como um componente muito ativo [2,40]. Outros autores reportaram, para esta substância isolada, as atividades antioxidante [34,47,55] e antitumoral [1,31]. Desta forma, o artepillin C aparece como um marcador químico em potencial para o controle de qualidade de "própolis de Baccharis dracunculifolia".…”

Cytotoxicity of Coprinopsis atramentaria extract, organic acids and their synthesized methylated and glucuronate derivatives

“…Drupanin and baccharin, two cinnamic acid derivatives, were reported as inhibitors of the growth of HeLa-60 cell lines by inducing apoptosis (Akao et al, 2003).…”