Assessment of the radioprotective effect of propolis in breast cancer patients undergoing radiotherapy. New perspective for an old honey bee product

Abstract

Background: Ionizing radiation is widely used for treatment of cancer. However, one of the limitations of using radiation is its toxic effects on normal tissue. Radiation damage to normal tissue can be partially reduced by the use of radio-protectors that scavenge free radicals produced during radiation. Recently, interest has increased in the development of potential drug of plant origin for the modification of radiation effects and has an advantage over the synthetic compounds in term of low or no toxicity and with minimum side effects. Propolis is apicultural product which is composed of nutritionally valuable substances and contains considerable amounts of polyphenol substances. Flavonoids and phenolic acids are the major classes of polyphenolic compounds. Because of its broad spectrum biological properties, the interest in propolis as harmless medicine has been increased. Aim of the work: The present study has been undertaken to evaluate the radio-protective effect of propolis supplementation in breast cancer (BC) patients undergoing radiotherapy. Subjects and methods: This study included 135 subjects divided into three main groups: Group I: 45 healthy females served as control group of matched age and menopausal status with the next malignant groups. Group II: 45 chemotherapy received breast cancer patients followed by radiation therapy only. Group III: 45 chemotherapy received breast cancer patients followed by radiation therapy plus propolis supplements. Two venous blood samples were collected from both breast cancer patients groups (Before and after radiotherapy) and one blood sample from matched controls. DNA damage in mononuclear cells was assessed by alkaline Comet assay. Serum was separated to measure ribonucleotide reductase M2 subunit (RRM2) by enzyme linked immunossorbent assay (ELISA). Malonaldhyde (MDA), total antioxidant capacity (TAC) and iron were assayed by colorimetric method. One ml blood sample was collected into EDTA tubes for complete blood picture analysis. Results: The present study showed that radiotherapy is accompanied by significant increase in Comet tail parameters (Tail length, % Tail DNA, Tail moment) in peripheral blood mononuclear cells of BC patients. While in the group of patients supplemented with propolis plus radiotherapy, propolis have the ability to reduce significantly the radiation induced DNA damage. Concerning RRM2 subunit, it was found that, although radiotherapy significantly down regulate RRM2 protein but still significantly higher than normal control value. On the other hand, the supplementation of propolis during radiotherapy caused a significant down regulation of RRM2 level and became within the normal control level. Furthermore, radiotherapy is accompanied by significant increase in serum MDA and significant decrease in serum TAC while after propolis supplementation plus radiotherapy, serum MDA and serum TAC significantly improved. Regarding serum iron and hematological parameters including hemoglobin (HB) concentration, white blood cells (WBCs) and platelets counts were significantly decreased after radiotherapy treatment alone while after radiotherapy plus propolis, these parameters significantly increased and became within the normal control level. Conclusions: Supplementation of propolis with radiotherapy treatment offers a quite measurable protection against DNA damage caused by ionizing radiation in BC patients leukocytes and inhibits RRM2 overexpression. Moreover, propolis has beneficial effects on the serum antioxidant capacity and improves the digestive utilization of iron and the regeneration efficiency of hemoglobin. Larger prospective studies are required to confirm our findings.

Keywords

• Breast cancer
• Radiotherapy
• Propolis
• Radio-protectors