Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways

Abstract

Breast cancer is the most commonly diagnosed cancer in females worldwide. Estimates from the World Health Organization (WHO) International Agency for Research on Cancer, suggest that globally, there were around 2.1 million new breast cancer cases and 627,000 deaths due to breast cancer in 2018. Among the subtypes of breast cancer, triple negative breast cancer (TNBC) is the most aggressive and carries the poorest prognosis, largest recurrence, and lowest survival rate. Major treatment options for TNBC patients are mainly constrained to chemotherapy, which can be accompanied by severe side effects. Therefore, development of novel and effective anti-cancer drugs for the treatment of TNBC are urgently required. Centipeda minima is a well-known traditional Chinese herbal medicine that has historically been used to treat rhinitis, sinusitis, relieve pain, and reduce swelling. Recent studies have shown that Centipeda minima exhibited efficacy against certain cancers, however, to date, no studies have been conducted on its effects in breast cancer. Here, we aimed to investigate the anti-cancer activity of the total extract of Centipeda minima (CME), and its underlying mechanism, in TNBC. In MDA-MB-231, we found that CME could significantly reduce cell viability and proliferation, induce apoptosis and inhibit cancer cell migration and invasion, in a dose and time-dependent manner. We showed that CME may potentially act via inhibition of multiple signaling pathways, including the EGFR, PI3K/AKT/mTOR, NF-κB, and STAT3 pathways. Treatment with CME also led to in vitro downregulation of MMP-9 activity and inhibition of metastasis. Further, we demonstrated that CME could significantly reduce tumor burden in MDA-MB-231 xenograft mice, without any appreciable side effects. Based on our findings, CME is a promising candidate for development as a therapeutic with high efficacy against TNBC.

Centipeda minima Extract Attenuates Dextran Sodium Sulfate-Induced Acute Colitis in Mice by Inhibiting Macrophage Activation and Monocyte Chemotaxis

“…Preparation of CME was conducted as described previously ( Chan et al, 2016 ; Lee et al, 2020 ). In brief, CM was air-dried and ground to a coarse powder.…”

Recent Advances in Anti-Metastatic Approaches of Herbal Medicines in 5 Major Cancers: From Traditional Medicine to Modern Drug Discovery

“…Especially, CS reduced the tumor area and nodules that spread to lung and liver by suppressing MMP-2 and MMP-9 [ 114 ]. Lee et al demonstrated that Centipeda minima ethanol extract (CME) significantly reduced cancer cell viability and suppressed cancer cell migration via AKT, NF-κB, and STAT3 signaling pathways [ 115 ]. Park et al presented that Cirsium japonicum var.…”

“…Meanwhile, there were some studies conducting experiments both on in vivo and in vitro. Since the results showed the difference between cell models and animal models, it is necessary to conduct further research and discussion about how the difference occurred [ 115 , 129 ]. In other words, some studies on bio-systemic mechanisms and interactions of herbal medicine are demanded.…”

The Prognostic Significance of Anisomycin-Activated Phospho-c-Jun NH2-Terminal Kinase (p-JNK) in Predicting Breast Cancer Patients’ Survival Time

“…Approximately 2.1 million people will be diagnosed with breast cancer in 2018, effectively making the ever-growing breast cancer population even larger ( Ferlay et al, 2018 ). Breast cancer is a heterogeneous disease that can be caused by many signaling pathways that are responsible for cell proliferation and cell apoptosis, such as PI3K/AKT/mTOR, JAK/STAT, PTEN/AKT/MDM2/p53, and AKT/NF-κB signaling pathway ( Wan et al, 2019 ; Lee et al, 2020 ; Martínez-Rodríguez et al, 2020 ; Narayanankutty, 2020 ; Nunnery and Mayer, 2020 ). Subsequently, due to genetic variability, different breast patients often exhibit varied susceptibility to different signaling pathways.…”