Chalcones and Dihydrochalcones Augment TRAIL-Mediated Apoptosis in Prostate Cancer Cells

Chalcones and dihydrochalcones exhibit chemopreventive and antitumor activity. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a natural endogenous anticancer agent. We examined the cytotoxic and apoptotic effect of chalcones and dihydrochalcones on TRAIL-mediated apoptosis in LNCaP prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was detected using annexin V-FITC by flow cytometry and fluorescence microscopy. The ΔΨm was evaluated using DePsipher staining by fluorescence microscopy. Our study showed that two tested chalcones (chalcone and 2’,6’dihydroxy-4’-methoxychalcone) and three dihydrochalcones (2’,6’-dihydroxy-4’4-dimethoxydihydrochalcone, 2’,6’-dihydroxy-4’-methoxydihydro- chalcone,  and 2’,4’,6’-trihydroxydihydrochalcone, called phloretin) markedly augmented TRAIL-induced apoptosis and cytotoxicity in LNCaP cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer

Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showed that all five tested chalcones: chalcone, licochalcone-A, isobavachalcone, xanthohumol, butein markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer

Dietary Flavonoids Sensitize HeLa Cells to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)

TRAIL is a promising candidate for cancer therapeutics that preferentially induces apoptosis in cancer cells. The combined treatment flavonoids with TRAIL might be promising as a chemoprevention and/or new therapy against malignant tumors. We examined the cytotoxic effect of dietary flavonoids in combination with TRAIL on HeLa cells. It was found that treatment with noncytotoxic concentration of some flavonoids significantly sensititizes to TRAIL induced death in HeLa cells. Our study demonstrated that flavone, apigenin and genistein markedly augmented TRAIL mediated cytotoxicity against HeLa, whereas kaempferol and quercetin produced no effect

Polyphenols Isolated from Propolis Augment TRAIL-Induced Apoptosis in Cancer Cells

Epidemiological data support the concept that phenols and polyphenols in diet are safe and nontoxic, and have long-lasting beneficial effects on human health. The potential target for complementary and alternative medicine (CAM) research has been on the discovery of natural compounds that can be used in the prevention and treatment of cancer. Propolis is one of the richest sources of plant phenolics (flavonoids and phenolic acids). The ethanolic extract of propolis (EEP) and its polyphenols possess immunomodulatory, chemopreventive, and antitumor effects. Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a  naturally occurring anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic to normal cells. Endogenous TRAIL plays a significant role in immunosurveillance and defense against cancer cells. However, as more tumor cells are reported to be resistant to TRAIL-mediated death, it is important to develop new strategies to overcome this resistance. EEP and polyphenols isolated from propolis have been shown to sensitize cancer cells to TRAIL-induced apoptosis. In this paper we demonstrate for the first time the crucial role of the main phenolics isolated from propolis in enhancing TRAIL-mediated death in tumor cells for cancer chemoprevention

TRAIL-induced apoptosis and expression of death receptor TRAIL-R1 and TRAIL-R2 in bladder cancer cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a member of TNF superfamily able to induce programmed death in cancer cells with no toxicity against normal tissues. TRAIL mediate apoptosis follows binding to the two death receptors, TRAIL-R1 (DR4) and/or TRAIL-R2 (DR5). In this study we investigated the cytotoxic and apoptotic effect of TRAIL on bladder cancer cells and the expression of death receptor TRAIL-R1 and TRAIL-R2 on the surface of these cancer cells. Three human bladder transitional cancer cell (TCC) lines - SW780, 647V and T24 were tested for TRAIL sensitivity. The bladder cancer cells were incubated with human soluble recombinant TRAIL. Cytotoxicity was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-dimethyltetrazolium bromide) and LDH (lactate dyhydrogenase) assays. Apoptosis was detected by flow cytometry with annexin V-FITC/propidium iodide and by fluorescence microscopy with Hoechst 33342/annexin V-FITC/Ethidium Homodimer. The cell surface expression of TRAIL death receptors on bladder cancer were determined using flow cytometry with phycoerythrin-conjugated monoclonal anti-human TRAIL-R1 and TRAIL-R2. Our investigations confirmed that SW780 cells were sensitive to TRAIL, and two other bladder cancer cell lines, 647V and T24, were resistant to TRAIL induced apoptosis. We therefore examined the expression of TRAIL death receptors on bladder cancer cell surfaces. We showed decreased expression of TRAIL-R2 receptor in TRAIL-resistant bladder cancer cells and increased expression of this death receptor in TRAIL-sensitive SW780 cells. The expression of TRAILR1 receptor was similar in all bladder cancer cell lines. TRAIL is one of the promising candidates for cancer therapeutics. However, some cancer cells are resistant to TRAIL-mediated apoptosis. It is therefore important to overcome this resistance for the clinical use of TRAIL in cancer therapy. TRAIL death receptors are attractive therapeutic targets in cancer treatment. The cytotoxic agents capable of up-regulating the expression of TRAIL-R1 and TRAIL-R2 can sensitize cancer cells to TRAIL induced apoptosis

Ethanolic Extract of Propolis Augments TRAIL-Induced Apoptotic Death in Prostate Cancer Cells

Prostate cancer is a commonly diagnosed cancer in men. The ethanolic extract of propolis (EEP) and its phenolic compounds possess immunomodulatory, chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/APO2L) is a naturally occurring anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effects of EEP and phenolic compounds isolated from propolis in combination with TRAIL on two prostate cancer cell lines, hormone-sensitivity LNCaP and hormone-refractory DU145. The cytotoxicity was evaluated by MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC/propidium iodide. The prostate cancer cell lines were proved to be resistant to TRAIL-induced apoptosis. Our study demonstrated that EEP and its components significantly sensitize to TRAIL-induced death in prostate cancer cells. The percentage of the apoptotic cells after cotreatment with 50 μg mL−1 EEP and 100 ng mL−1 TRAIL increased to 74.9 ± 0.7% for LNCaP and 57.4 ± 0.7% for DU145 cells. The strongest cytotoxic effect on LNCaP cells was exhibited by apigenin, kaempferid, galangin and caffeic acid phenylethyl ester (CAPE) in combination with TRAIL (53.51 ± 0.68–66.06 ± 0.62% death cells). In this work, we showed that EEP markedly augmented TRAIL-mediated apoptosis in prostate cancer cells and suggested the significant role of propolis in chemoprevention of prostate cancer

Antitumoral and antiangiogenic activity of Portuguese propolis in in vitro and in vivo models

Propolis, a natural product, has important biological properties, however, studies with Portuguese propolis are scarce. Thus, we aimed to characterize the chemical composition and the antitumoural and antiangiogenic activities of a sample from Pereiro (Portugal). The chemical profile of our propolis sample (P10.EE) is similar to the poplar propolis type. P10.EE decreased cell viability of different tumour cells, being less cytotoxic against non-tumoural cells. P10.EE decreased MDA-MB-231 and DU145 cell proliferation and migration, with cell cycle changes and increased cell death. The increased glucose consumption and lactate production in MDA-MB-231 cells is explained by an increased expression of different metabolism-related proteins. P10.EE induced a decrease in HBMEC cells total biomass and proliferation and decreased vessel sprouting in the chicken chorioallantoic membrane. Additionally, P10.EE potentiates paclitaxel effect in MDA-MB-231 and DU145 cells. Concluding, P10.EE can be a good candidate for cancer drug development since it affects different characteristics that dictate tumorigenesis.This work was supported by the Life and Health Sciences Research Institute, University of Minho, Portugal, and Fundacao para a Ciencia e Tecnologia (FCT) (SFRH/BD/5199712012 to V.M.G.), through Fundo Europeu de Desenvolvimento Regional-QREN-COMPETE, projects PTDC/AAC-CLI1098308/2008 and PTDC/AAC-CLI/11809212010 and also CERNAS (project PEst-OE/AGR/UI0681/2011)