الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Breast cancer is a growing problem because it is one of the most common causes of cancer-related death in women around the globe. Accumulating evidence over the past decade has established the existence of a cancer stem cells (CSCs) subpopulation within breast cancers that are responsible for tumor initiation, progression and drug resistance. Therefore, therapeutic strategies targeting these cells might increase the effectiveness of anticancer therapy and could provide a reduction of its toxicity. Currently, common pluripotency markers such as OCT4, SOX2, and NANOG are extensively studied in relation to CSCs.
Currently used cancer therapy is effective against cancer, but also causes cell death in normal cells, thereby causing severe side effects in patients. There is a serious need for the development of more effective and safer alternatives to chemotherapy and radiation. Natural health products have been used for centuries to treat various forms of diseases, although many of the therapeutic benefits have not been scientifically studied for their efficacy and safety.
Our objective was to investigate the cytotoxic effect of ionizing radiation and berberine on MCF-7 cell viability and their effect on the expression of stem cell markers OCT4 and SOX2 in human breast cancer cell line MCF-7.
This study is an in vitro study employing the human breast cancer cell line MCF-7 (cultured as spheroids) which was divided into four groups:
group 1: MCF-7 spheroids as untreated control.
group 2: MCF-7 spheroids treated with ionizing radiation alone (exposed to various doses 2, 4, 6 and 8 Gy).
group 3: MCF-7 spheroids treated with berberine chloride alone (various concentrations 25, 50, 100 and 150 μM).
group 4: MCF-7 spheroids treated with berberine chloride (at IC50 = 100 μM) + various doses of ionizing radiation (2, 4, 6 and 8 Gy).
The MTT assay was taken to assess the cytotoxicity of berberine chloride treatment, ionizing radiation treatment and combination of berberine chloride and ionizing radiation on MCF-7 spheroids. The qRT-PCR was used to evaluate the expression of OCT4 and SOX2 genes after the berberine chloride treatment, ionizing radiation treatment and a combination of berberine chloride and ionizing radiation in MCF-7 spheroids.
Our results showed that:
Ionizing radiation significantly decreased the cell viability of MCF-7 spheroids and reduced OCT4 and SOX2 genes expression after 24 h treatment at all doses (2,4,6 and 8 Gy).
Berberine significantly decreased the cell viability of MCF-7 spheroids and significantly lowered OCT4 and SOX2 genes expression after 24 h treatment at 50, 100 and 150 μM and insignificantly decreased the cell viability of MCF-7 cells and OCT4 and SOX2 genes expression at concentration 25 μM.
Summary
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Combining berberine treatment at IC50 (100 μM) with ionizing radiation leads to a significant reduction in cell viability and OCT4 and SOX2 genes expression which was noticed with increasing the radiation dose when compared to the untreated control group.
There is a significant difference in MCF-7 cell viability and OCT4 and SOX2 genes expression between ionizing radiation only treated group and the group treated with combined radiation and berberine at IC50.