Abstract
Elaeagnus angustifolia (EA) is a medicinal plant used for treating several human diseases in the Middle East. Meanwhile, the outcome of EA extract on HER2-positive breast cancer remains nascent. Thus, we herein investigated the effects of the aqueous EA extract obtained from the flowers of EA on two HER2-positive breast cancer cell lines, SKBR3 and ZR75-1. Our data revealed that EA extract inhibits cell proliferation and deregulates cell-cycle progression of these two cancer cell lines. EA extract also prevents the progression of epithelial-mesenchymal transition (EMT), an important event for cancer invasion and metastasis; this is accompanied by upregulations of E-cadherin and β-catenin, in addition to downregulations of vimentin and fascin, which are major markers of EMT. Thus, EA extract causes a drastic decrease in cell invasion ability of SKBR3 and ZR75-1 cancer cells. Additionally, we found that EA extract inhibits colony formation of both cell lines in comparison with their matched control. The molecular pathway analysis of HER2 and JNK1/2/3 of EA extract exposed cells revealed that it can block HER2 and JNK1/2/3 activities, which could be the major molecular pathway behind these events. Our findings implicate that EA extract may possess chemo-preventive effects against HER2-positive breast cancer via HER2 inactivation and specifically JNK1/2/3 signaling pathways.
Highlights
Breast cancer (BC) commonly affects women worldwide, comprising 25% of cancer cases [1].There are several risk factors, both environmental and genetic, associated with the onset of breast cancer [2]
Treatment with Elaeagnus angustifolia (EA) extract reduced the number of proliferating HER2-positive breast cancer cells in a dose-dependent manner (Figure 1); notably, concentrations of 100 and 200 μL/mL showed a substantial decrease in cell viability of SKBR3 and ZR75-1 by 50% and 75%, respectively
Treatment with EA extract reduced the number of proliferating HER2-positive breast cancer cells in a dosedependent manner (Figure 1); notably, concentrations of 100 and 200 μL/mL showed a substantial decrease in cell viability of SKBR3 and ZR75-1 by 50% and 75%, respectively
Summary
Breast cancer (BC) commonly affects women worldwide, comprising 25% of cancer cases [1]. There are several risk factors, both environmental and genetic, associated with the onset of breast cancer [2]. Gene-expression-profiling studies classified breast cancer into five molecular subtypes: Luminal (A and B), HER2, basal-like, and normal-like, using hierarchical cluster analysis [3]. HER2-positive breast cancer accounts for 20–25% and is associated with aggressive phenotype, poor prognosis, and survival rate, in addition to increased recurrence [4]. Systemic management modalities for HER2-positive breast cancer include chemotherapy, radiation, and targeted anti-HER2 treatment modalities [4,5,6,7]. The treatment is generally effective in the early stages of therapy, Molecules 2020, 25, 4240; doi:10.3390/molecules25184240 www.mdpi.com/journal/molecules
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