Abstract
BackgroundBreast cancer is the most frequently diagnosed cancer, and no effective treatment solution has yet been found. The number of studies based on the research of novel natural compounds in the treatment of breast cancer has been increasing in recent years. The anticancer properties of natural compounds are related to the regulation of microRNA (miRNA) expression. Therefore, changing the profile of miRNAs with the use of natural products is very important in cancer treatment. However, the role of vulpinic acid and related miRNAs in breast cancer progression remains unknown. Vulpinic acid, methyl (as2E)-2-(3-hydroxy-5-oxo-4-phenylfuran-2-ylidene)-2 phenylacetate, is a natural product extracted from the lichen species and shows an anticancer effect on different cancer cells.MethodsThis study examines the effects of vulpinic acid on the miRNA levels of breast cancer (MCF-7) cells and its relationship with cell proliferation and apoptosis levels. The antiproliferative effect of vulpinic acid was screened against MCF-7 breast cancer cells and MCF-12A breast epithelial cells using the xCELLigence real-time cell analysis system. We analyzed the altered miRNA expression profile in MCF-7 breast cancer cells versus MCF-12A cells following their response to vulpinic acid through microarray analysis. The microarray analysis results were confirmed through quantitative real-time PCR and bioinformatics analysis.ResultsThe results of the miRNA array and bioinformatic analyses demonstrated that 12 miRNAs were specifically responsive to vulpinic acid in MCF-7 breast cancer cells. This is the first study to reveal that vulpinic acid inhibits the expression of 12 miRNAs and suppresses breast cancer cell proliferation. The study also revealed that vulpinic acid may downregulate the expression of 12 miRNAs by repressing the FOXO-3 gene. The miRNA targets were mainly found to play a role in the apoptosis, cell cycle and MAPK pathways. Moreover, Bcl-2, Bax, procaspase-3 and procaspase-9 protein levels were assessed by western blot analysis for validation of apoptosis at the protein level.ConclusionThis study revealed the molecular mechanisms of vulpinic acid on breast cancer and showed that vulpinic acid regulates apoptosis signaling pathways by decreasing the expression of miRNAs. The miRNA expression patterns illuminate the underlying effect of vulpinic acid in breast cancer treatment.Graphical
Highlights
Breast cancer is the most frequently diagnosed cancer, and no effective treatment solution has yet been found
The IC50 value of vulpinic acid obtained using the real-time cell analysis (RTCA) system was 18.0 ± 0.02 μM for MCF-7 breast cancer cells based on the sigmoidal dose–response formula (Fig. 1A)
The obtained results indicate that MCF-7 breast cancer cells were sensitive to vulpinic acid, and the viability of MCF-7 breast cancer cells significantly decreased after treatment with the vulpinic acid
Summary
Breast cancer is the most frequently diagnosed cancer, and no effective treatment solution has yet been found. Breast cancer is the most commonly diagnosed and malignant cancer subtype among women [1]. It is a heterogeneous disease with different phenotypes based on gene expression analysis [2]. Cancer treatment types can be classified into radiation therapy, surgery, endocrine therapy, targeted therapy and chemotherapy [4] These treatment types can reduce the effect of malignancy but raise the risk of further diseases. While chemotherapeutics destroy cancer cells, they damage normal cells In addition to this side effect, when the patient develops resistance to the highly cytotoxic drug, two or more cytotoxic drugs are mixed, resulting in more physical and psychological side effects for the human [4]. There is a particular need to understand the biological mechanisms underlying breast cancer and to develop novel, effective options for the diagnosis, prognosis and treatment of breast cancer
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