الفهرس 
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Abstract
Cancer continues to be a major public health problem in both developed and developing countries, as millions of people are diagnosed with cancer every year. It is a leading cause of death globally and accounted for 8.8 million deaths (around 1 in 6 deaths is due to cancer) in 2015. Squamous cell carcinoma (SCC) is the most frequent malignant tumour of the head and neck region, and the sixth leading cancer by incidence worldwide. There are 500000 new cases a year worldwide.
The standard treatment modalities against cancer are series of interventions and approaches, including surgery, radiotherapy, chemotherapy and psychosocial support. The aim of the treatment is curing the disease or prolonging life considerably and improving the patient’s quality of life212. Chemotherapy is delivering cytotoxic drugs systemically so that they can reach and kill the tumour cells. However, most of these drugs cause series side effects as they are toxic to other viable cells of the human body. And, thus, need to be given at suboptimal levels.
Due to this resistance to anti-cancer agents, it was crucial to find new anticancer compounds in order to develop novel drugs that can circumvent the resistance mechanisms. Recently, honey has been under intense investigation for their use in cancer therapy. Phenolic compounds are considered among the main components contributing to the antioxidant and other useful properties of honey.
The concept of dual therapy of anti-cancer drugs with natural products has become a very appealing strategy in novel drug discovery. Phytochemicals from natural sources existing in our daily diet are now being exploited for chemopreventive purposes. Several reports have described the ability of
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these naturally derived compounds to modulate the process of carcinogenesis.
The aim of the current study was to investigate the in vitro effect of four different types of honey and its phenolic contents on the human laryngeal squamous carcinoma cell line and to determine the possible modulation of the activity of 5-fluorouracil by natural bee honey on the same types of cells.
They antiproliferative effect was evaluated with MTT assay, while the mechanisms of action were assessed with flow cytometry assay, DNA fragmentation assay and nuclear morphomertic analysis.
In this study, Individual treatment of Hep-2 cells with different types of honey resulted in a time-dependent decrease in cell viability. Nuclear morphomertic analysis revealed a time dependent decrease in the mean values of NAF of the Hep-2 cells treated with different types of honey when compared to control cells. Cells treated with Eucalyptus honey shows the lowest value which means highest apoptosis inducing activity. Fragmentation of DNA also was observed in Hep-2 cells following treatment with different types of honey.
Moreover, using flow cytometry assay revealed a time-dependent promotion of apoptotic activity for all samples (in comparison to the control), again Eucalyptus honey was found to induce the highest apoptotic activity compared with the others.
According to the previous findings; the examined four samples of honey showed antiproliferative and apoptosis promotion anticancer activities, and this could be correlated with the content of polyphenols in honeys, given that Eucalyptus honey showed the utmost anticancer activity which has a much higher TPC than other samples.
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5-fluorouracil is a commonly used chemotherapeutic agent to treat many cancer types, but their use is largely restricted due to its serious side effects. In the present study, we found that treatment of Hep-2 cancer cells with 5-fluorouracil combined with Ellagic acid displayed synergism in inhibiting its proliferation. , suggesting that administration of Ellagic acid together with the standard chemotherapeutic drug may decrease its cytotoxic side effects.