Predicted molecular targets and pathways for germacrone, curdione, and furanodiene in the treatment of breast cancer using a bioinformatics approach

Kong, Qi; Ma, Yan; Yu, Jie; Chen, Xiuping

doi:10.1038/s41598-017-15812-9

Cited by 36 publications

(21 citation statements)

References 36 publications

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“…At present, many databases made a significant contribution to the development of systems biology, such as the Bioinformatics Analysis Tool for Molecular mechanism of TCM (BATMAN-TCM) developed by Liu (Liu et al, 2016). BATMAN-TCM was applied in the study exploring the mechanism of Curcuma longa L (E'Zhu) in the treatment of breast cancer (Kong et al, 2017). In this article, we try to explore the pharmacological mechanism of KX in treating RA and explain how the drugs combination of herbs works on reducing adverse reactions.…”

Section: Introductionmentioning

confidence: 99%

Kunxian Capsule for Rheumatoid Arthritis: Inhibition of Inflammatory Network and Reducing Adverse Reactions Through Drug Matching

Tang

Zeng

et al. 2020

Front. Pharmacol.

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Tripterygium wilfordii Hook.f and Tripterygium hypoglaucum (H.Lév.) Hutch is effective herbs to prevent aggravation of Rheumatoid arthritis (RA). However, both of them show severe side effects in the reproductive system and other systems. Kunxian Capsule (KX), a Traditional Chinese Medicine (TCM) patent prescription, comprised of 4 herbs, including H.Lév. Hutch, is reported to be an available prescription in treating RA with fewer side effects as compares to Tripterygium tablets. To reveal the pharmacological mechanism of KX in RA treatment and side effect alleviation, we collected related information of KX from open-access databases and performed various analyses. 1354 targets were identified in KX. These targets were enriched in the calcium signaling pathway, cAMP signaling pathway, cGMP-PKG signaling pathway and PI3K-AKT signaling pathway, forming biological functions, such as cofactor binding, coenzyme binding, etc. These pathways or functions mostly affect cell cycle, differentiation, and maturation of Th17 cells, macrophage, and synovial fibroblast. These targets also act on the IL-17 signaling pathway, Th17 cell differentiation signaling pathway and TNF signaling pathway, which is related to inflammation response inhibition. Next, a disease network was constructed, which indicated IMPDH2, MTHFD1 are the key genes answering for the side effects of H.Lév. Hutch. The side effect-related genes lead to the negative regulation of nucleic acid, which could be restored by the rest 3 herbs through some positive amino acid metabolism. In conclusion, KX is a relatively safe alternative approach in RA intervention.

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Section: Introductionmentioning

confidence: 99%

Kunxian Capsule for Rheumatoid Arthritis: Inhibition of Inflammatory Network and Reducing Adverse Reactions Through Drug Matching

Tang

Zeng

et al. 2020

Front. Pharmacol.

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“…Feng et al reported that in the antiviral test in vitro, germacrone showed high antiporcine reproductive respiratory syndrome virus (PRRSV) infection activity by inhibiting the replication process of PRRSV [17]. Recent studies have found that germacrone has a significant anti-cancer effect, can inhibit the progress of colorectal cancer, liver cancer, breast cancer, lung cancer and other cancers, and has the characteristics of high efficiency and low toxicity [18][19][20]. Lim et al found that germacrone inhibited breast cancer progression by inhibiting estrogen receptor α and synergizing with other antitumor drugs 5-fluorouracil and methotrexate [21].…”

Section: Introductionmentioning

confidence: 99%

Germacrone protects against oxygen-glucose deprivation/reperfusion injury by inhibiting autophagy processes in PC12 cells

Zhang

Wang

et al. 2020

BMC Complement Med Ther

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Background: Germacrone is an anti-inflammatory ingredient in the Chinese medicine zedoary turmeric. The purpose of this study was to explore the protective mechanism of germacrone against PC12 cells injury caused by oxygen-glucose deprivation/reperfusion (OGD/R). Methods: OGD/R injury model of PC12 cells was established by using OGD/R (2 h/24 h). The cell viability was assessed by MTT assay and LDH release. The ultrastructure of cells was observed by transmission electron microscopy (TEM). The expression of autophagy related proteins in cells was determined by Western Blot. Results: The results of ultrastructural observation showed that PC12 cells damaged by OGD/R showed typical autophagy characteristics. In addition, OGD/R observably up-regulated the expression of autophagy related proteins: the class III type phosphoinositide 3-kinase (PI3K III), light chain 3(LC3), and Beclin-1 in PC12 cells, and inhibited the expression of the class I type phosphoinositide 3-kinase (PI3K I), Protein kinase B (Akt), the mammalian target of rapamycin (mTOR), and B-cell lymphoma 2(Bcl-2) proteins. Furthermore, germacrone increased the cell viability of OGD/R-damaged PC12 cells by down-regulating the expression of LC3 protein in cells in a concentration-dependent manner. More importantly, germacrone significantly inhibited the expression of PI3K III, LC3, and Beclin-1 in OGD/R-injured PC12 cells, and up-regulated the expressionof PI3K I, Akt, mTOR, and Bcl-2 proteins in cells, and this inhibited or up-regulated effect was reversed by PI3K I inhibitor (ZSTK474). Conclusion: The above results indicated that germacrone could inhibit the autophagy effect in OGD/R injury model of PC12 cells, the mechanism of inhibition was regulated by PI3K III/Beclin-1/Bcl-2 and PI3K I/Akt/mTOR pathways, thereby improving the cell viability of PC12 cells and playing a neuroprotective role, which provided a new drug for the treatment of OGD/R.

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“…Some studies have shown that the anticancer activity of Saussurea costus is mainly due to its major components sesquiterpenoids [36,37]. Germacrone is a sesquiterpene and has certain anticancer effects on glioma, retinoblastoma, breast cancer, liver cancer, prostate cancer, and colon cancer [12][13][14][15][16][17]38]. However, the pharmacological effects and mechanisms of germacrone against human ESCC are still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Germacrone Inhibits Cell Proliferation and Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cells

Zhang

Jiang

Guo

et al. 2020

BioMed Research International

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Germacrone, a natural 10-membered monocyclic sesquiterpene with three double bonds and a ketone, was isolated from the roots of traditional Chinese medicine Saussurea costus (SC). The pharmacological value and intrinsic mechanism of germacrone in the treatment of esophageal squamous cell carcinoma (ESCC) are still unclear. Therefore, in this study, we further explored the internal molecular mechanism by which germacrone exerts its antiproliferation and antimigration ability against ESCC. 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assays showed that germacrone dose-dependently inhibited the proliferation of ESCC cells. Flow cytometry analysis (FACS) and wound healing experiments on germacrone treated ESCC cells showed that germacrone could induce apoptosis and inhibit the migration of ESCC cells in a dose-dependent manner. In the study on the mechanism of action of germacrone in antiesophageal cancer, we found that germacrone increased the ratio of Bax/Bcl-2 in the cytoplasm of ESCC, resulting in the activation of Caspase-9 and Caspase-3 and decreased the expression of Grp78, thereby reducing the inhibition of Caspase-12 and Caspase-7. In addition, we found that germacrone also inhibited STAT3 phosphorylation in a dose-dependent manner. In conclusion, we determined that germacrone exerted an antiesophageal effect through intrinsic apoptotic signaling pathways and by inhibiting STAT3 activity in ESCC cells.

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Predicted molecular targets and pathways for germacrone, curdione, and furanodiene in the treatment of breast cancer using a bioinformatics approach

Cited by 36 publications

References 36 publications

Kunxian Capsule for Rheumatoid Arthritis: Inhibition of Inflammatory Network and Reducing Adverse Reactions Through Drug Matching

Kunxian Capsule for Rheumatoid Arthritis: Inhibition of Inflammatory Network and Reducing Adverse Reactions Through Drug Matching

Germacrone protects against oxygen-glucose deprivation/reperfusion injury by inhibiting autophagy processes in PC12 cells

Germacrone Inhibits Cell Proliferation and Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cells

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