Caffeic acid phenethyl ester induces mitochondria-mediated apoptosis in human myeloid leukemia U937 cells

Abstract

Caffeic acid phenyl ester (CAPE), a biologically active ingredient of propolis, has several interesting biological properties including antioxidant, anti-inflammatory, antiviral, immunostimulatory, anti-angiogenic, anti-invasive, anti-metastatic and carcinostatic activities. Recently, several groups have reported that CAPE is cytotoxic to tumor cells but not to normal cells. In this study, we investigated the mechanism of CAPE-induced apoptosis in human myeloid leukemia U937 cells. Treatment of U937 cells with CAPE decreased cell viability in a dose-dependent and time-dependent manner. DNA fragmentation assay revealed the typical ladder profile of oligonucleosomal fragments in CAPE-treated U937 cells. In addition, as evidenced by the nuclear DAPI staining experiment, we observed that the nuclear condensation, a typical phenotype of apoptosis, was found in U937 cells treated with 5 microg/ml of CAPE. Therefore, it was suggested that CAPE is a potent agent inducing apoptosis in U937 cells. Apoptotic action of the CAPE was accompanied by release of cytochrome C, reduction of Bcl-2 expression, increase of Bax expression, activation/cleavage of caspase-3 and activation/cleavage of PARP in U937 cells, but not by Fas protein, an initial mediator in the death signaling, or by phospho-eIF2 alpha and CHOP, crucial mediators in ER-mediated apoptosis. From the results, it was concluded that CAPE induces the mitochondria-mediated apoptosis but not death receptors- or ER-mediated apoptosis in U937 cells.

The Ethanol Extract of Polish Propolis Exhibits Anti-Proliferative and/or Pro-Apoptotic Effect on HCT 116 Colon Cancer and Me45 Malignant Melanoma Cells In Vitro Conditions.

“…Similar results were obtained by Jin et al [34], who performed a similar experiment on human leucoma cells line U937 and stated that CAPE has a citotoxic activity non-related to concentration and time exposure on cancer cells. Using the DAPI dye application, they observed the changes characteristic for apoptosis in cells nuclei.…”

Cytotoxic constituents of propolis inducing anticancer effects: a review

“…HT-29 Hernandez et al [42] Caffeic acid phenethyl ester A549, LS 180, HeLa, NCTC clone L 929, M12.C3.F6 Chen et al [43] Caffeic acid phenethyl ester BxPC-3, PANC-1 Lee et al [44] Caffeic acid phenethyl ester SK-Hep1 Lee et al [45] Caffeic acid phenethyl ester HepG2 Lee et al [46] Caffeic acid phenethyl ester Daoy Jin et al [47] Caffeic acid phenethyl ester U937 Jung et al [48] Caffeic acid phenethyl ester MCF7, MDA 231 Lin et al [49] Caffeic acid phenethyl ester C6 expression levels was verified in cells from leukaemia patients treated with Manisa propolis, due to chrysin. [57] The cytotoxic effect of polyphenolic/flavonoid compounds on different leukaemia cell lines was evaluated using five different flavonoids (quercetin, caffeic acid, chrysin, naringenin and naringin) and five leukaemia cell lines (MOLT, JURKAT, HL-60, RAJI and U937).…”

Effect of Turkish pollen and propolis extracts on caspase-3 activity in myeloid cancer cell lines

“…Jin et al [17] investigated the mechanism of CAPE-induced apoptosis in U937 cells. They showed that CAPE decreased cell viability in dose-dependent and time dependent manner, DNA fragmentation and nuclear condensation in cancer cells and apoptotic action accompanied by release of cytochrome c, reduction of Bcl-2 expression, increase of Bax expression [17].…”