Differential Apoptotic Effects of Bee Product Mixtures on Normal and Cancer Hepatic Cells

Abstract

Most effective anticancer drugs normally generate considerable cytotoxicity in normal cells; therefore, the preferential activation of apoptosis in cancer cells and the reduction of toxicity in normal cells is a great challenge in cancer research. Natural products with selective anticancer properties used as complementary medicine can help to achieve this goal. The aim of the present study was to analyze the effect of the addition of bee products [propolis (PR) or royal jelly (RJ) or propolis and royal jelly (PR+RJ), 2–10%] to thyme (TH) and chestnut honeys (CH) on the differential anticancer properties, mainly the cytotoxic and pro-apoptotic effects, in normal and cancer hepatic cells. The cytotoxic effects of samples were analyzed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay (0–250 mg/mL) and the effects on apoptosis were analyzed using cell cycle analysis, TdT-dUTP terminal nick-end labeling (TUNEL) assay, DR5 (Death Receptor 5) and BAX (BCL-2-Associated X) activation, and caspases 8, 9, and 3 activities. Both honey samples alone and honey mixtures had no or very little apoptotic effect on normal cells. Antioxidant honey mixtures enhanced the apoptotic capacity of the corresponding honey alone via both extrinsic and intrinsic pathways. Of all the samples, chestnut honey enriched with 10% royal jelly and 10% propolis (sample 14, CH+10RJ+10PR) showed the highest apoptotic effect on tumor liver cells. The enrichment of monofloral honey with bee products could be used together with conventional anticancer treatments as a dietary supplement without side effects. On the other hand, it could be included in the diet as a natural sweetener with high added value.

Exploring the in vitro potential of royal jelly against glioblastoma and neuroblastoma: impact on cell proliferation, apoptosis, cell cycle, and the biomolecular content

“…50,51 In contrast, even application of 100 mg mL −1 RJ did not cause apoptosis in HepG2 and WRL-68 cells. 52 This contradiction may be related to the different origins and compositions of the royal jelly samples since the environmental and biological factors, including season, plant type, ambient conditions, and the time after larval transfer, could all have a huge impact on their content. 53 The increased late apoptotic percentage of both glioblastoma and neuroblastoma cell lines proved that application of 10 mg mL −1 RJ stimulated the cell apoptosis.…”

Yemeni Sidr Honey Inhibits Cell Proliferation and Promotes Apoptosis in Human Cancer and Mouse-Derived Cell Lines

“…Some reports have shown that gallic acid, quercetin, and ellagic acid are able to inhibit cancer cell proliferation at levels similar to what is present in YSH [4,12.18,46]. Other studies have also identified YSH components such as carvacol, thymol, catechin, and some sulfatide compounds as being active in killing cancer cells [46][47][48]. A more comprehensive study of a larger number of different honey samples with a wider range of identified standards would be useful for verifying that YSH samples have a more unique pattern of chemical composition which can be used to distinguish them from other types of honey and which could be used to identify likely anti-cancer components.…”

Selenomethionine Attenuated H2O2-Induced Oxidative Stress and Apoptosis by Nrf2 in Chicken Liver Cells

“…A TUNEL assay was used to measure DNA destruction in the final stages of apoptosis [ 27 ]. The overnight-cultured cells were treated or co-treated with H 2 O 2 for 24 h. Untreated LMHs served as the control.…”