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

Abstract

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.

A Comparative Study on Propolis and Pollen Extracts: Chemical Profile Analysis, Antioxidant and Anticancer Activity

“…The cytotoxic activity of propolis extracts is generally higher than pollen extracts. Many reports have indicated that different types of propolis extracts significantly inhibit cell growth and reduce the differentiation or proliferation of tumor cells (Zliszka et al, 2011;Khalil, 2006). Vatansever et al (2010) reported cytotoxicity of EEP at a concentration of 125 μg/mL to MCF-7 cell line also they found that cytotoxic effects of seven EEP samples collected from the same location is different.…”

Ethanolic extract of Brazilian green propolis sensitizes prostate cancer cells to TRAIL-induced apoptosis

“…The expression of the DRs, TRAIL-R1 or TRAIL-R2, and pro-apoptotic or anti-apoptotic proteins in cancer cells is involved in TRAIL-resistance (17)(18)(19). We and others have shown that TRAIL-resistant prostate cancer cells can be sensitized by bioactive polyphenols (7)(8)(9)(10)(11)(12)(13)(14).…”

“…Propolis cannot be used as a raw material, so it must be purified by extraction to remove the inert material and preserve the polyphenolic fraction (20). The ethanolic extract of propolis (EEP) has attracted the interest of researchers in the last decade because of its many biological properties, such as antioxidant, immunomodulatory, chemopreventive and anticancer effects (11,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). These data suggest that propolis regulates multiple signalling pathways and has the potential to improve health and prevent diseases.…”

“…we previously reported the efficacy of European propolis in increasing the apoptotic activity of TRAIL in HeLa cervical, DU145 and LNCaP prostate cancer cells (11,28). We then tested the apoptotic and cytotoxic effects of Brazilian EEP in combination with TRAIL on LNCaP prostate cancer cells and investigated the molecular mechanisms by which propolis helps LNCaP cells overcome TRAIL resistance.…”

Combined effect of viscous dissipation and thermal radiation on fluid flows over a non-linearly stretched permeable wall

“…Unfortunately, most of chemical radioprotectors (AET, WR 2721, WR 1065) have shown toxic side effects that limit their use in medical practice [4]. Propolis has shown protect against the induction of apoptosis by radiation; since it is an imunomodulator, it has antioxidative and cytotoxic activities, antitumor activities, and scavenges free radicals produced by the indirect effect of ionizing radiation [2,[7][8][9][10][11][12]. Moreover, several reports have demonstrated the ability of EEP to protect mice against gamma irradiation preventing exaggerated inflammatory response [9], promoting high survival in mice [10], protecting their whole blood cells, and also diminishing primary DNA damage in mice [4,13].…”