Abstract 3553: Manuka honey induced apoptosis in hepatocellular carcinoma through inhibition of Wnt/b-catenin and ERK1/2

Abstract

Hepatocellular carcinoma (HCC) is one of the most malignant tumors that affect individuals worldwide and most therapies are still badly guaranteed due to its potential toxicity. Nowadays, there is increasing awareness focused on identification of naturally occurring anticancer agents derived from food or natural products, as honey which possess a high content of polyphenols and flavonoids.

Manuka honey (MH) has been recognized by its biological properties as antimicrobial agent, anti-inflammatory activity, antioxidant efficacy and has a potent role in wound healing. Also Manuka honey possesses anticancer property in inhibiting proliferation of malignant tumor. However, its antiproliferative and apoptotic effect on human hepatocellular carcinoma cells (HepG2) remain unclear. Therefore, the current study focused mainly on investigating the anticancer properties of MH and its mechanism of action. Cell viability was evaluated by MTT assay, microscopic examination was undertaken to monitor the morphological alternation of HepG2 cells after treatment. Furthermore, the antiproliferative and apoptosis mechanism was estimated by the level of caspase-3 activity and a possible cross talk between protein expression of total ERK1/2, oncogenic β-catenin, cyclin D1, proapoptotic protein, Bax and poly (ADP-ribose) polymerase (PARP) is explained by observing their expression levels by western blot analysis. The combination effect of MH with doxorubicin (DOX) was also investigated.

Our results revealed that MH treatment for 48 h showed a substantially proliferation inhibition of HepG2 cells in a dose dependent manner with IC₅₀ concentration of (6.92± 0.005%) and induces dramatic morphological changes of cells, which considered as characteristics of apoptosis. Consistently, MH or combined treatment showed a significant increase in caspase-3 activity in treated HepG2 cells when compared to untreated cells. In addition, the expression levels of total ERK1/2, oncogenic β-catenin and cyclin D1 were significantly downregulated with MH treatment, whereas the expression level of Bax and PARP cleavage were remarkably upregulated after 48h. In addition, a combination of MH and doxorubicin led to a significant synergistic effect.

Collectively, for our knowledge, the present study provides the first report on the anticancer activity of MH on HCC cells. Our study may provide a targeting therapy for HCC by inhibition of Wnt/ β-catenin and ERK1/2 signalling pathways and induction of apoptosis was detected by Bax up-regulation and PARP cleavage after 48h. Moreover, MH can be considered as a promising naturally occurring anticancer compound that can be used as an effective adjuvant therapeutic for treatment of HCC.

Citation Format: Heba R. Al Refaey, Ahmed S. Sultan. Manuka honey induced apoptosis in hepatocellular carcinoma through inhibition of Wnt/b-catenin and ERK1/2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3553.