Eupalinolide J Suppresses the Growth of Triple-Negative Breast Cancer Cells via Targeting STAT3 Signaling Pathway

Lou, Chenghua; Chen, Yan; Zhang, Jie; Yang, Bo; Zhao, Huajun

doi:10.3389/fphar.2019.01071

Cited by 18 publications

(25 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TNBC is the most aggressive form of breast cancer, lacking the expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. STAT3 has been shown to play an important pro-oncogenic role in TNBC [82] and to be a potential therapeutic target [83], with studies indicating the presence of hyperactivated STAT3, driven by the phosphorylation of tyrosine 705. In addition, S727phosphorylated mitochondrial STAT3 has also been implicated in breast cancer [84].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial STAT3 regulates antioxidant gene expression through complex I‐derived NAD in triple negative breast cancer

et al. 2021

View full text Add to dashboard Cite

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor with roles in inflammation and tumorigenicity. A fraction of STAT3 localizes in mitochondria, where it augments tumorigenesis via regulation of mitochondrial functions, including modulation of respiration and redox status. We show a novel mechanism for mitochondrial STAT3 regulation of redox homeostasis in triple-negative breast cancer cells. Loss of STAT3 diminished complex I dehydrogenase activity and impaired NAD+ regeneration, leading to impaired expression of glutathione biosynthetic genes and other antioxidant genes. Expressing mitochondrially restricted STAT3 or replenishment of the cellular NAD pool restored antioxidant gene expression, as did complementation of the NADH dehydrogenase activity by expression of the STAT3-independent yeast dehydrogenase, NDI1. These NAD-regulated processes contributed to malignant phenotypes by promoting clonal cell growth and migration. Proximity interaction and protein pull-down assays identified three components of complex I that associated with mitochondrial STAT3, providing a potential mechanistic basis for how mitochondrial STAT3 affects complex I activity. Our data document a novel mechanism through which mitochondrial STAT3 indirectly controls antioxidant gene regulation through a retrograde NAD+ signal that is modulated by complex I dehydrogenase activity.

show abstract

Section: Discussionmentioning

confidence: 99%

Mitochondrial STAT3 regulates antioxidant gene expression through complex I‐derived NAD in triple negative breast cancer

et al. 2021

View full text Add to dashboard Cite

show abstract

“…(3) Eupalinolide J, the active compound and a sesquiterpene lactone of Eupatorium lindleyanum , promotes the degradation of STAT3 in TNBC cell lines MDA-MB-231 and MDA-MB-468 in vivo mouse xenograft model and in vitro. 89 …”

Section: Resultsmentioning

confidence: 99%

A Review of Natural Therapies Potentially Relevant in Triple Negative Breast Cancer Aimed at Targeting Cancer Cell Vulnerabilities

Webb

Kukard

2020

Integr Cancer Ther

View full text Add to dashboard Cite

We reviewed the research into the mechanisms of growth of triple negative breast cancer (TNBC) based on laboratory pre-clinical studies that have shaped understanding of the disease over the past decade. In response to these findings, we propose an approach to potentially prevent cancer metabolic adaptation and recurrence. This paper collates pre-clinical results, first to determine the tumor’s mechanisms of growth and then to source natural substances that could potentially suppress those mechanisms. The results from in vivo and in vitro studies of TNBC were combined first to select 10 primary mechanisms (Hypoxia-inducible factor 1α, Hedgehog, MAPK, MTAP, NF-κ B, Notch, P13K, STAT3, and Wnt signaling pathways plus p53 and POL2A gene expression) that promote TNBC growth, and second to propose a treatment array of 21 natural compounds that suppress laboratory models of TNBC via these mechanisms. We included BRCA mutations in the review process, but only pathways with the most preclinical studies utilizing natural products were included. Then we outlined potential biomarkers to assess the changes in the micro-environment and monitor biochemical pathway suppression. This suppression-centric aim targets these mechanisms of growth with the goal of potentially halting tumor growth and preventing cancer cell metabolic adaptation. We chose TNBC to demonstrate this 5-step strategy of supplementary therapy, which may be replicated for other tumor types.

show abstract

“…Because apoptotic cell death plays an important role in cancer treatment, 30,31 we next investigated whether thymol has an effect on the apoptosis of CRC cells. Hoechst 33258 staining was used to evaluate morphological changes occurring in the nucleus.…”

Section: Thymol Induces Apoptosis and Cell Cycle Arrest In Crc Cellsmentioning

confidence: 99%

<p>Thymol Isolated from <em>Thymus vulgaris</em> L. Inhibits Colorectal Cancer Cell Growth and Metastasis by Suppressing the Wnt/β-Catenin Pathway</p>

Zeng

Che

Zhang

et al. 2020

DDDT

View full text Add to dashboard Cite

Purpose: Colorectal cancer (CRC) is one of the most commonly occurring cancers and is associated with high morbidity and mortality. Nevertheless, there is currently no safe and effective treatment for this condition. Thymol is a phenolic compound that is recognized as safe for use in food as well as medical and cosmetic fields. Increasing evidence has indicated that thymol exerts prominent antitumor effects in a variety of cancers, including CRC. However, how thymol elicits these effects on CRC and the associated underlying mechanisms remains unclear. Methods: HCT116 and Lovo cells were treated with different concentrations of thymol. Cell Counting Kit-8 (CCK-8) and transwell migration and invasion assays were used to evaluate cell proliferation, migration, and invasion, respectively. Cell apoptosis and cell cycle distribution were measured by flow cytometry. RT-qPCR, Western blot, and immunohistochemistry were used to detect the expression of related genes and their protein products. Results: In this study, we tested the antitumor activity of thymol extracted from a Chinese medicinal herb, Thymus vulgaris L. We show that thymol treatment in vitro inhibited cell proliferation and induced apoptosis and cell cycle arrest in CRC. Furthermore, in vivo treatment with 75 and 150 mg/kg thymol led to a significant decrease in tumor volume. Thymol administration induced CRC cell apoptosis through activation of the BAX/Bcl-2 signaling pathway. In addition, thymol suppressed CRC cell epithelial-mesenchymal transition (EMT), invasion, and metastasis via inhibiting the activation of the Wnt/β-catenin pathway, both in vitro and in vivo. Conclusion: Thymol may prevent CRC progression through inhibition of the Wnt/β-catenin signaling pathway, highlighting its potential as a novel therapeutic option for the treatment of CRC.

show abstract

Eupalinolide J Suppresses the Growth of Triple-Negative Breast Cancer Cells via Targeting STAT3 Signaling Pathway

Cited by 18 publications

References 49 publications

Mitochondrial STAT3 regulates antioxidant gene expression through complex I‐derived NAD in triple negative breast cancer

Mitochondrial STAT3 regulates antioxidant gene expression through complex I‐derived NAD in triple negative breast cancer

A Review of Natural Therapies Potentially Relevant in Triple Negative Breast Cancer Aimed at Targeting Cancer Cell Vulnerabilities

<p>Thymol Isolated from <em>Thymus vulgaris</em> L. Inhibits Colorectal Cancer Cell Growth and Metastasis by Suppressing the Wnt/β-Catenin Pathway</p>

Contact Info

Product

Resources

About