Abstract
Bruceine D (BD) is a natural compound extracted from a Chinese herb Brucea javanica that has been used for anti-inflammatory and anti-cancer treatment. However, little is reported about BD's effects in breast cancer tumorigenesis. In this paper, we aimed to investigate the effect of BD in breast cancer and elucidate the potential mechanism of BD by integrated multiple databases. Our data suggested BD inhibited MCF-7 and MDA-MB-231 cells proliferation and promoted cells apoptosis. We integrated multiple bioinformatics analysis strategies to identify genes, hub modules and pathways associated with BD treatment. Three key pathways, including AMIT_SERUM_RESPONSE_40_MCF10A, BILD_HRAS_ONCOGENIC_SIGNATURE, and NAGASHIMA_NRG1_SIGNALING_UP were identified to be associated with therapeutic effects of BD in breast cancer. Additionally, we validated the key genes by using quantitative real-time PCR and western blot. In conclusion, these findings revealed potential molecular mechanisms of BD to treat breast cancer by affecting AMIT_SERUM_RESPONSE_40_MCF10A, BILD_HRAS_ONCOGENIC_SIGNATURE, and NAGASHIMA_NRG1_SIGNALING_UP pathways and regulating expression of ZFP36, EGR1, and FOS.
Highlights
Breast cancer is one of the most common malignancies with high rates of morbidity and mortality in women [1,2,3,4]
MCF-7 cells showed more sensitivity to Bruceine D (BD) than MDA-MB-231. These results indicate that the inhibition of BD on MCF-7 and MDA-MB-231 cells proliferation is dose and time dependent
D, the ratio of apoptotic cells was clear increased as the concentration of BD increased. These findings indicate that BD could induce S phase cell cycle arrest and apoptosis in MCF-7 and MDA-MB-231 cells in a dose-dependent manner
Summary
Breast cancer is one of the most common malignancies with high rates of morbidity and mortality in women [1,2,3,4]. Over the past 20 years, the incidence rate of breast cancer is increasing in China [5,6,7]. Natural compounds have been considered as an important source of anti-tumor drugs [12, 13]. Bruceine D (BD) is a natural compound derived from a herb of Brucea javanica. It has been reported that BD has good pharmacological activities including cytotoxic effects on cancer cell, anti-inflammatory and hypoglycemic activities [2, 14,15,16,17]. We used breast cancer cells MCF-7 and MDA-MB-231 to test the effects of BD. Results illustrated that the Bruceine D Breast Cancer intervention with BD significantly inhibits the proliferation and induces apoptosis of MCF-7 and MDA-MB-231 cells
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