Antiangiogenic activity of Tripterygium wilfordii and its terpenoids

He, Ming; Liu, Lin; Ge, Wei; Shaw, Pang Chui; Jiang, Ren‐Wang; Wu, Li-Wha; But, Paul Pui Hay

doi:10.1016/j.jep.2008.09.033

Cited by 81 publications

(54 citation statements)

References 41 publications

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“…There are two important subpopulations of HSP90's clients, kinases and nuclear TFs. The effects of celastrol on the kinase sub-population, such as Cdks and ERK are firmly confirmed in several cellular models (He et al 2009b;Kim et al 2009c, Salminen et al 2010, but celastrol's effects on TFs sub-population HSP90's client are not well-established, despite of the work on several members in Class I nuclear receptor family (Chadli et al 2010). At present, whether celastrol has broad effects on TFs sub-population clients remains contrary.…”

Section: Introductionmentioning

confidence: 95%

Celastrol regulates multiple nuclear transcription factors belonging to HSP90's clients in a dose- and cell type-dependent way

Zhang

Cao

et al. 2010

Cell Stress and Chaperones

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Celastrol, a novel HSP90 inhibitor, has recently attracted much attention due to its potential in multiple applications, such as anti-inflammation use, degenerative neuron disease relief, and tumor management. At present, the studies in celastrol's effects on HSP90's clients have focused on the kinase sub-population, while another key sub-population, nuclear transcription factors (TFs), is not being well-explored. In this study, we observe the effects of celastrol on 18 TFs (belonging to HSP90 clients) in three human cell lines: MCF-7 (breast cancer), HepG2 (hepatoma), and THP-1 (monocytic leukemia). The results show that at least half of the detectable TFs were affected by celastrol, though the effect patterns varied with cell type and dosage. Bi-directional regulations of some TFs were identified, a phenomenon not yet seen with other HSP90 inhibitors. Celastrol's capability to affect multiple TFs was consistent with its altering HSP90/TFs interactions and disrupting HSP90/Hop interaction, in addition to the reported damaging HSP90/Cdc37 interaction. This work confirms, for the first time, that celastrol has broad effects on TFs belonging to HSP90's clients, casts new light on understanding these reported actions, and suggests new possible applications for celastrol, such as diabetes management.

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Section: Introductionmentioning

confidence: 95%

Celastrol regulates multiple nuclear transcription factors belonging to HSP90's clients in a dose- and cell type-dependent way

Zhang

Cao

et al. 2010

Cell Stress and Chaperones

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“…Triptolide is a diterpenoid triepoxide and the principal active ingredient of Tripterygium wilfordii Hook. f. (Leigongteng) (He et al, 2009). It has been reported to have pharmacological and biochemical properties in the treatment of rheumatoid arthritis and several other autoimmune and inflammatory diseases, including immune complex nephritis and systemic lupus erythematosus (Lu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Triptolide Inhibits Proliferation and Induces Apoptosis of Human Melanoma A375 Cells

Tao¹,

Zhang²,

Ma³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Triptolide, a diterpenoid obtained from Tripteryglum wilfordii Hook.f, has attracted interest for its antitumor activities against human tumor cell lines in recent years. This report focuses on anti-proliferative and pro-apoptotic activities in human melanoma A375 cells assessed by CCK8 assay, Hoechst 33258 staining and flow cytometry. In addition, triptolide-induced arrest in the S phase was also observed. Caspase assays showed the apoptosis induced by triptolide was caspase-dependent and probably through intrinsic apoptotic pathways. Furthermore, expression of NF-kB (p65) and its downstream factors such as Bcl-2, Bcl-X L was down-regulated. Taken together, the data indicate that triptolide inhibits A375 cells proliferation and induces apoptosis by a caspase-dependent pathway and through a NF-kB-mediated mechanism.

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“…[19][20][21][22][23][24][25][26][27][28][29] Different varieties of drugs tested in zebrafish elicit similar responses to those observed in mammalian models, [30][31][32] considering the remarkable homology in the molecular and signaling pathways involved in vessel formations between zebrafish and mammals. [33][34][35] Compared with other drug screening systems, the dominant advantages of the zebrafishbased assay include: (1) it is suitable for high-throughput drug screening; (2) it offers more relevant information to humans compared to other invertebrate models and in vitro cell lines, while it costs much less than mammalian systems.…”

mentioning

confidence: 99%

Anti-angiogenic Activity of Erxian Decoction, a Traditional Chinese Herbal Formula, in Zebrafish

Tong

Kwok

et al. 2012

Biological & Pharmaceutical Bulletin

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Erxian Decoction (EXD), a traditional Chinese herbal formula, has been used to treat menopausal symptoms and other aging diseases for several decades. Recently, our laboratory found that EXD could inhibit the proliferation of breast cancer cells. This activity may be mediated by anti-angiogenic action. To investigate the anti-angiogenic activity of EXD, its inhibitory effect on blood vessel formation was evaluated using both wild type and transgenic zebrafish embryos with fluorescent vasculature in vivo. Both semi-quantitative and real-time quantitative polymerase chain reaction (qPCR) were carried out to evaluate the effect of EXD on the expression of several genes closely associated with angiogenesis in zebrafish. EXD was found to inhibit vessel formation in zebrafish embryos in a dose-and time-dependent manner. Furthermore, it reduced the mRNA expression of vascular endothelial growth factor A (VEGF-A) and the protein level of hypoxia inducible factor 1α (HIF-1α) in the embryos, suggesting the involvement of HIF-1 mediated VEGF-A signaling pathway in the anti-angiogenic action of EXD. The anti-angiogenic activity of EXD provides new insights to its clinical application and may in the future lead to the development of potential drugs for treating various cancers, especially in menopausal period.Key words angiogenesis; zebrafish; Erxian Decoction; vascular endothelial growth factor A; hypoxia inducible factor 1αErxian Decoction (EXD), a traditional Chinese herbal formula, consists of six Chinese herbs: Epimedium sagittatum (SIEB. et ZUCC) MAXIM. (Berberidaceae, whole herb), Curculigo orchioides GAERTN. (Hypoxidaceae, rhizome), Morinda officinalis HOW (Rubiaceae, root), Angelica sinensis (OLIV.) DIELS (Umbelliferae, root), Phellodendron chinense SCHNEID. (Rutaceae, bark) and Anemarrhena asphodeloides BUNGE (Anthericaceae, rhizome). It has been used to treat osteoporotic disorders, 1) menopausal symptoms 2,3) and other aging diseases 4) in elderly patients for several decades.Angiogenesis is the formation of new blood vessels from existing ones. This complex process involves an extensive interplay between cells, soluble factors, and the extracellular matrix (ECM), which includes the proliferation and migration of endothelial cells. 5) Under particular conditions which include wound healing, embryonic development and tissue or organ regeneration, angiogenesis occurs at specific moments, which are regulated by stimulatory and inhibitory factors. 6,7)However, under certain pathological conditions such as the growth of solid tumors, tumor metastasis, rheumatoid arthritis and diabetic retinopathy, the angiogenic process takes place in a poorly controlled manner. 5,8,9) Plenty of traditional Chinese medicinal herbs are rich sources of compounds with anti-inflammatory and anti-carcinogenic properties. There are prominent evidences suggesting the co-dependence of chronic inflammation and angiogenesis. Both of them associate with the increase of cellular infiltration and proliferation, and are influenced by regulatory gro...

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Antiangiogenic activity of Tripterygium wilfordii and its terpenoids

Cited by 81 publications

References 41 publications

Celastrol regulates multiple nuclear transcription factors belonging to HSP90's clients in a dose- and cell type-dependent way

Celastrol regulates multiple nuclear transcription factors belonging to HSP90's clients in a dose- and cell type-dependent way

Triptolide Inhibits Proliferation and Induces Apoptosis of Human Melanoma A375 Cells

Anti-angiogenic Activity of Erxian Decoction, a Traditional Chinese Herbal Formula, in Zebrafish

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