Celastrol Inhibits Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Interleukin-6 via Downregulating Nuclear Factor-κB (NF-κB)

Yan, Fei; Wu, Zihong; Li, Zihui; Liu, Li

doi:10.12659/msm.922814

Cited by 16 publications

(6 citation statements)

References 32 publications

(32 reference statements)

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“…Medicinal plants containing bioactive constituents are a great resource for modern drug development, and Tripterygium wilfordii is one of them. Its major constituent celastrol has numerous pharmacological actions including antiinflammatory, anti-obesity, anti-diabetic, and anti-cancer activities (Cascão et al, 2017;Chen et al, 2018;Hou et al, 2020;Yan et al, 2020;Lu et al, 2021). However, there are multiple challenges in translating traditional herbal medicines and their active constituents to modern drug therapies.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

“…Thus, in view of a multitude of advantages offered by the nanotechnology, celastrol nanoformulations have been widely explored and reported in the literature. Specifically, celastrol nanoformulations have shown significant benefits in several therapeutic applications against prostate cancer, breast and pancreatic cancers, nonsmall-cell lung cancer, ovarian cancer, and human colon cancer and other applications in treating rheumatoid arthritis, polycystic kidney disease, inflammation, and Parkinson's disease (schematically depicted in Figure 1) (Abbas et al, 2007;Salminen et al, 2010;Yadav et al, 2010;Mou et al, 2011;Kim et al, 2013;Chang et al, 2018;Qi et al, 2018;Zha et al, 2018;Lin et al, 2019;Song et al, 2019;Yan et al, 2020). This review summarizes such state-of-the-art therapeutic applications of celastrol nanoformulations in the subsequent sections.…”

Section: Introductionmentioning

confidence: 99%

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Nanotechnology-Based Celastrol Formulations and Their Therapeutic Applications

et al. 2021

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Celastrol (also called tripterine) is a quinone methide triterpene isolated from the root extract of Tripterygium wilfordii (thunder god vine in traditional Chinese medicine). Over the past two decades, celastrol has gained wide attention as a potent anti-inflammatory, anti-autoimmune, anti-cancer, anti-oxidant, and neuroprotective agent. However, its clinical translation is very challenging due to its lower aqueous solubility, poor oral bioavailability, and high organ toxicity. To deal with these issues, various formulation strategies have been investigated to augment the overall celastrol efficacy in vivo by attempting to increase the bioavailability and/or reduce the toxicity. Among these, nanotechnology-based celastrol formulations are most widely explored by pharmaceutical scientists worldwide. Based on the survey of literature over the past 15 years, this mini-review is aimed at summarizing a multitude of celastrol nanoformulations that have been developed and tested for various therapeutic applications. In addition, the review highlights the unmet need in the clinical translation of celastrol nanoformulations and the path forward.

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Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nanotechnology-Based Celastrol Formulations and Their Therapeutic Applications

et al. 2021

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“…Celastrol is the main bioactive ingredient extracted from traditional Chinese medicinal herb Tripterygium wilfordii [22]. Studies have shown that celastrol has potential cytotoxicity in a variety of tumor cells [21][22][23]. Recent studies have also found that celastrol can significantly increase the intracellular ROS levels, leading to apoptosis, cell cycle arrest, and autophagy of cancer cells [24,25].…”

Section: Introductionmentioning

confidence: 99%

Celastrol elicits antitumor effects by inhibiting the STAT3 pathway through ROS accumulation in non-small cell lung cancer

et al. 2022

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Background Non-small cell lung cancer (NSCLC) is the most common lung cancer with high mortality across the world, but it is challenging to develop an effective therapy for NSCLC. Celastrol is a natural bioactive compound, which has been found to possess potential antitumor activity. However, the underlying molecular mechanisms of celastrol activity in NSCLC remain elusive. Methods Cellular function assays were performed to study the suppressive role of celastrol in human NSCLC cells (H460, PC-9, and H520) and human bronchial epithelial cells BEAS-2B. Cell apoptosis levels were analyzed by flow cytometry, Hoechst 33342, caspase-3 activity analysis, and western blot analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometry and fluorescence microscope. Expression levels of endoplasmic reticulum (ER) stress-related proteins and phosphorylated signal transducer and activator of transcription 3 (P-STAT3) were identified via western blot analysis. A heterograft model in nude mice was employed to evaluate the effect of celastrol in vivo. Results Celastrol suppressed the growth, proliferation, and metastasis of NSCLC cells. Celastrol significantly increased the level of intracellular ROS; thus, triggering the activation of the ER stress pathway and inhibition of the P-STAT3 pathway, and eventually leading to cell apoptosis, and the effects were reversed by the pre-treatment with N-Acetyl-l-cysteine (NAC). Celastrol also suppressed tumor growth in vivo. Conclusion The outcomes revealed that celastrol plays a potent suppressive role in NSCLC in vitro and in vivo. Celastrol induces apoptosis via causing mitochondrial ROS accumulation to suppress the STAT3 pathway. Celastrol may have potential application prospects in the therapy of NSCLC.

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“…Nitric oxide (NO) has been suggested to possess both antitumor and protumor properties, depending on tissue type and timing [ 38 ]. MDA-MB-468 cells treated with T. mastichina EO showed a significant decrease in the production of nitrite, the main indicator of NO concentration, compared to the control after both treatment times.…”

Section: Discussionmentioning

confidence: 99%

GC, GC/MS Analysis, and Biological Effects of Essential Oils from Thymus mastchina and Elettaria cardamomum

Vuković

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Obradović

et al. 2022

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Spanish marjoram (Thymus mastichina) and cardamom (Elettaria cardamomum) are traditional aromatic plants with which several pharmacological properties have been associated. In this study, the volatile composition, antioxidative and antimigratory effects on human breast cancer (MDA-MB-468 cell line), antimicrobial activity, and antibiofilm effect were evaluated. Results obtained via treatment of human breast cancer cells generally indicated an inhibitory effect of both essential oils (EOs) on cell viability (after long-term treatment) and antioxidative potential, as well as the reduction of nitric oxide levels. Antimigratory effects were revealed, suggesting that these EOs could possess significant antimetastatic properties and stop tumor progression and growth. The antimicrobial activities of both EOs were determined using the disc diffusion method and minimal inhibition concentration, while antibiofilm activity was evaluated by means of mass spectrometry. The best antimicrobial effects of T. mastichina EO were found against the yeast Candida glabrata and the G+ bacterium Listeria monocytogenes using the disc diffusion and minimal inhibitory concentration methods. E. cardamomum EO was found to be most effective against Pseudomas fluorescens biofilm using both methods. Similarly, better effects of this oil were observed on G− compared to G+ bacterial strains. Our study confirms that T. mastichina and E. cardamomum EOs act to change the protein structure of older P. fluorescens biofilms. The results underline the potential use of these EOs in manufactured products, such as foodstuffs, cosmetics, and pharmaceuticals.

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Celastrol Inhibits Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Interleukin-6 via Downregulating Nuclear Factor-κB (NF-κB)

Cited by 16 publications

References 32 publications

Nanotechnology-Based Celastrol Formulations and Their Therapeutic Applications

Nanotechnology-Based Celastrol Formulations and Their Therapeutic Applications

Celastrol elicits antitumor effects by inhibiting the STAT3 pathway through ROS accumulation in non-small cell lung cancer

GC, GC/MS Analysis, and Biological Effects of Essential Oils from Thymus mastchina and Elettaria cardamomum

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