Caffeic Acid Phenethyl Ester and Ethanol Extract of Propolis Induce the Complementary Cytotoxic Effect on Triple-Negative Breast Cancer Cell Lines

Abstract

Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells' susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity of ethanol extract of propolis (EEP) and its derivative caffeic acid phenethyl ester (CAPE) towards two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and Hs578T, by implementation of the MTT and lactate dehydrogenase (LDH) assays. The morphological changes of breast carcinoma cells were observed following exposure to EEP and CAPE. The IC50 of EEP was 48.35 µg·mL for Hs578T cells, whereas the CAPE IC50 was 14.08 µM and 8.01 µM for the MDA-MB-231 and Hs578T cell line, respectively. Here, we report that propolis and CAPE inhibited the growth of the MDA-MB-231 and Hs578T lines in a dose-dependent and exposure time-dependent manner. EEP showed less cytotoxic activity against both types of TNBC cells. EEP and, particularly, CAPE may markedly affect the viability of breast cancer cells, suggesting the potential role of bioactive compounds in chemoprevention/chemotherapy by potentiating the action of standard anti-cancer drugs.

Mechanisms involved in the cytotoxic action of Brazilian propolis and caffeic acid against HEp-2 cells and modulation of P-glycoprotein activity

“…Several researches have shown the anticarcinogenic and proapoptotic effects of CAPE, but little is known regarding Caf effects. CAPE and Caf are different molecules with different physical, chemical and functional properties.…”

Different propolis samples, phenolic content, and breast cancer cell lines: Variable cytotoxicity ranging from ineffective to potent

“…Today, the positive contribution of propolis to health, which are via its antimicrobial, anti-inflammatory, regenerative, immunomodulatory, antioxidant and antimutagenic effects have been proven by scientific studies (1)(2)(3)(4)6). One of the most important biological attributes of propolis has been pointed out by various studies to be the anticarcinogenic effects (5,7,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28).…”

“…On the other hand, although it was not investigated in this study, a derivate of caffeic acid, CAPE is considered a major pharmaceutical component of propolis (49) and evaluated more extensively in the literature. CAPE was reported to inhibit the growth of the BCCLs, MDA-MB-231 (28,29), Hs578T (28), MCF-7 (29), and SK-BR-3 (29) in a dosedependent and exposure time-dependent manner (28). It was also reported that CAPE reduces expression of growth and transcription factors, including NF-κB (50) and induces cell cycle arrest and apoptosis (51).…”

“…Recently, in vitro cell culture studies on the cytotoxic effects of propolis extracts from different regions have shown noteworthy findings (15)(16)(17)(18)(19)(20)(21)(22). In this context, the anticarcinogenic effects of propolis originated from diverse geographies were studied on breast cancer cell lines (BCCLs) (23)(24)(25)(26)(27)(28)(29). Lately, the chemical compositions, biological properties, and therapeutic activities of Turkey propolis have been analyzed using chromatographic and molecular biological techniques (30)(31)(32)(33)(34) and the typical Turkey poplar propolis samples displayed high phenolic and flavonoid contents (32).…”

Bisnaphthalimidopropyl diaminodicyclohexylmethane induces DNA damage and repair instability in triple negative breast cancer cells via p21 expression

“…In this study, the mechanism of action of a novel bisnaphthalimidopropyl derivative, BNIPDaCHM, was investigated in one of the most commonly studied poly(ADP-ribose) polymerase inhibitors [32], and also, propolis and its derivative caffeic acid phenethyl ester [33], to name a few.…”