RESUMO
Propolis cinnamic acid derivatives have a number of biological activities including anti-oxidant and anti-cancer ones. In this study, we aimed to elucidate the mechanism of the anti-cancer activity of 3 representative propolis cinnamic acid derivatives, i.e., Artepilin C, Baccharin and Drupanin in human colon cancer cell lines. Our study demonstrated that these compounds had a potent apoptosis-inductive effect even on drug-resistant colon cancer cells. Combination treatment of human colon cancer DLD-1 cells with 2 of these compounds, each at its IC20 concentration, induced apoptosis by stimulating both intrinsic and extrinsic apoptosis signaling pathways. Especially, Baccharin plus Drupanin exhibited a synergistic growth-inhibitory effect by strengthening both intrinsic and extrinsic apoptotic signaling transduction through TRAIL/DR4/5 and/or FasL/Fas death-signaling loops and by increasing the expression level of miR-143, resulting in decreased expression levels of the target gene MAPK/Erk5 and its downstream target c-Myc. These data suggest that the supplemental intake of these compounds found in propolis has enormous significance with respect to cancer prevention.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cinamatos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Própole/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Inibidores de Caspase/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cinamatos/química , Cinamatos/isolamento & purificação , Sinergismo Farmacológico , Proteína Ligante Fas/genética , Feminino , Fluoruracila/farmacologia , Humanos , Medicina Tradicional , Modelos Biológicos , Compostos Organoplatínicos/farmacologia , Oxaliplatina , Fenilpropionatos/química , Fenilpropionatos/isolamento & purificação , Fenilpropionatos/farmacologia , Própole/análogos & derivados , Própole/química , Própole/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Ligante Indutor de Apoptose Relacionado a TNF/genética , Tricotecenos/química , Tricotecenos/isolamento & purificação , Tricotecenos/farmacologia , Regulação para CimaRESUMO
Investigation of the chemical constituents of Rhizoma Cyperi (Cyperus rotundus Linneus)resulted in the isolation of novel enantiomeric andmeso-stilbene trimers [i.e., (+)- and (−)-(E)-cyperusphenol A (1, 2 respectively) and (E)-mesocyperusphenol A (3)], a trimer bearing a novelhexacyclic ring system [cyperusphenol B (5)], aswell as knownstilbenoids (cyperusphenols C (4)and D (6), scirpusins A (7) and B (8), and piceid (9)) and luteolin. HPLC was used for the opticalresolution of 1 and 2 as well as for the identification of cooccurrence of enantiomers of 7. Thestructures of the isolates were established by spectroscopic analyses, including a detailed NMRspectroscopic investigation. The isolates were evaluated in terms of their antiproliferative activityemploying the Jurkat cell line (human T-cell leukemia cells), while the IC50 potencies of aracemate of 1 and 2, 3, 5, and 6 were estimated as 27.4, 40.5, 26.4, and 26.3 µM, respectively. Thesuppression of cell growth by 6 was due to the induction of apoptosis,whichwas characterized bynuclear changes and PARP-1 cleavage determined bywestern blotting.We also evaluated the freeradical scavenging activity of the isolates.