Abstract
Triple-negative breast cancers (TNBCs) are hard-to-treat breast tumors with poor prognosis, which need to be treated by chemotherapy. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in proliferation, metastasis, and invasion of cancer cells. Therefore, research on searching for promising compounds with metabolism that suppress phosphorylation or transcription of STAT3 in TNBC cells is important. Farfarae Flos is well known as a traditional medicine for treating inflammation. However, few studies have shown that sesquiterpenoids from Farfarae Flos have an anticancer effect. In this study, efficient separation methods and an MTT assay were conducted to isolate an anticancer compound from Farfarae Flos against TNBC MDA-MB-231 cells. Here, 7β-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a compound isolated from Farfarae Flos showed a potent cytotoxic effect on MDA-MB-231 cells. ECN inhibited JAK–STAT3 signaling and suppressed the expression of STAT3 target genes. In addition, ECN induced apoptosis through both extrinsic and intrinsic pathways. Furthermore, we investigated that ECN inhibited the growth of tumors by intraperitoneal administration in mice injected with MDA-MB-231 cells. Therefore, ECN can be an effective chemotherapeutic agent for breast cancer treatment.
Highlights
Breast cancer is the most common cancer and the leading cause of cancer-related death among women [1]
We examined the level of phosphorylation EGFR and Janus kinase (JAKs) proteins in MDA-MB-231 cells treated treated with ECN to determine whether the inhibitory effect of ECN on Signal transducer and activator of transcription 3 (STAT3) phosphorylation is with ECN to determine whether the inhibitory effect of ECN on STAT3 phosphorylation is associated associated with the suppression of upstream signaling pathways
We demonstrated that ECN inhibited the JAK–STAT3 signaling pathway inducing apoptosis of Triple-negative breast cancers (TNBCs) MDA-MB-231 cells
Summary
Breast cancer is the most common cancer and the leading cause of cancer-related death among women [1]. Researchers have identified hormonal, lifestyle, and environmental factors that may increase the risk of breast cancer [2]. It is not clear how to define the causes of developing cancer [3,4]. Further improvements in cancer biology have allowed the development of systemic treatments, hormonal therapies, and target drugs, better understanding of breast cancer is needed to refine disease mechanisms and molecular characteristics to improve drug development and treatment approaches [5]. Gene expression analysis identified breast cancer subtypes, including basal-like, human epidermal growth factor receptor type
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