Anti-angiogenic effect of Tanshinone IIA involves inhibition of matrix invasion and modification of MMP-2/TIMP-2 secretion in vascular endothelial cells

Tsai, Ming-Yen; Yang, Rong-Chi; Wu, Hsiao‐Ting; Pang, Jong‐Hwei S.; Huang, Sheng‐Teng

doi:10.1016/j.canlet.2011.06.031

Cited by 61 publications

(42 citation statements)

References 28 publications

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“…Moreover, proliferation markers, such as Ki67 and PCNA, were significantly decreased in the Tan IIA - treated group, compared to controls. Angiogenesis is suggested to be critical for a solid tumor reach few millimeters in size3. The inhibition of microvessel formation resulting from limited supply of nutrients and oxygen is therefore responsible for reducing tumor size in Tan IIA-treated mice, as confirmed by CD31 immunostaining.…”

Section: Discussionmentioning

confidence: 75%

“…Angiogenesis is a crucial process in supplying the required nutrients and oxygen during the development, growth as well as progression and metastasis of cancer. It allows metastatic tumor cells to leak into the circulation and to reside in the organs by breaking through the basement membrane and endothelial cells (EC) to come into a new vessel34. Vascular branching signals released from ECs regulate mitochondrial biogenesis in the neovascularization.…”

mentioning

confidence: 99%

“…Tanshinone IIA (Tan IIA) is one of the major diterpenes extracted from Danshen with anti-oxidative13, anti-inflammatory14 and anti-atherosclerotic15 effects. Our previous study3 found that Tan IIA with anti-angiogenic effects, both in vivo and in vitro , was associated with modulation with the secretion between matrix metalloproteinase 2 (MMP-2) and TIMP metallopeptidase inhibitor 2 (TIMP-2) in an opposite way and resulted in the decreased MMP-2 activity of vascular endothelial cells without cytotoxicity. In addition, Tan IIA was reported to inhibit growth through cell cycle arrest and apoptosis via intrinsic and extrinsic pathways on various cancer cell lines161718.…”

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confidence: 99%

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Tanshinone IIA induces intrinsic apoptosis in osteosarcoma cells both in vivo and in vitro associated with mitochondrial dysfunction

Huang

et al. 2017

Sci Rep

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Tanshinone IIA (Tan IIA), a phytochemical derived from the roots of Salvia miltiorrhiza, has been shown to inhibit growth and induce apoptosis in various cancer cells. The association of its inhibitory effect on the primary malignant bone tumor, osteosarcoma, with mitochondrial dysfunction remains unclear. This study aimed to investigate the anti-proliferative effects of Tan IIA on human osteosarcoma 143B cells both in vitro and in vivo. Administration of Tan IIA to NOD-SCID mice implanted with 143B cells led to significant inhibition of tumor development. The inhibition of proliferation, migration, and invasion was observed in 143B cells treated with Tan IIA. The tumor proliferation markers, Ki67 and PCNA, were suppressed and apoptosis by TUNEL assay was activated respectively. Apoptosis in the Tan IIA-treated 143B cells and xerograft mice was associated with the activation of caspase cascade via the modulation of Bcl-2 family. The CD31 was inhibited in Tan IIA-treated xenografts to indicate anti-neovasculization. Tan IIA administration resulted in a significant decrease in the mitochondrial fusion proteins, Mfn1/2 and Opa1, as well as an increase in the fission protein Drp1. We concluded that mitochondrial dysfunction associated with dynamic change was involved in apoptosis and anti-angiogenesis elicited by Tan IIA.

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Section: Discussionmentioning

confidence: 75%

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confidence: 99%

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confidence: 99%

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Tanshinone IIA induces intrinsic apoptosis in osteosarcoma cells both in vivo and in vitro associated with mitochondrial dysfunction

Huang

et al. 2017

Sci Rep

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“…Thus, in present study, we intended to identify compound 10 whether only elicited an angiogenesis effect under pathological conditions of angiogenesis deficiencies such as ischemic cerebral and heart diseases or not. In addition, the anti-cancer activities of numerous natural tanshinones had been well characterized in several pre-clinical studies [45], [46], [47]. Therefore, we performed a pilot study testing the anti-proliferation effect of 10 compared to Tan IIA, CPT and Tan I in three cancer cell lines (MCF-7, MDA-231 and A549).…”

Section: Resultsmentioning

confidence: 99%

In Vivo Angiogenesis Screening and Mechanism of Action of Novel Tanshinone Derivatives Produced by One-Pot Combinatorial Modification of Natural Tanshinone Mixture from Salvia Miltiorrhiza

Zhang

et al. 2014

PLoS ONE

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BackgroundNatural products present in low quantity in herb medicines constitute an important source of chemical diversity. However, the isolation of sufficient amounts of these low abundant constituents for structural modification has been a challenge for several decades and subsequently halts research on the utilization of this important source of chemical entities for drug discovery and development. And, pro-angiogenic therapies are being explored as options to treat cardio-cerebral vascular diseases and wound healing recently. The present study investigates the pro-angiogenic potential of tanshinone derivatives produced by one-pot synthesis using zebrafish model.Methodology/Principal FindingsIn order to address the difficulty of chemical modification of low abundant constituents in herb medicines, a novel one-pot combinatorial modification was used to diversify a partially purified tanshinone mixture from Salvia miltiorrhiza. This led to the isolation of ten new imidazole-tanshinones (Compounds 1–10) and one oxazole-tanshinone (Compound 11), the structures of which were characterized by spectroscopic methods in combination with single-crystal X-ray crystallographic analysis. The angiogenesis activities of the new tanshinone derivatives were determined in an experimental model of chemical-induced blood vessels damage in zebrafish. Of all the tested new derivatives, compound 10 exhibited the most potent vascular protective and restorative activity with an EC50 value of 0.026 µM. Moreover, the mechanism underlying the pro-angiogenesis effect of 10 probably involved the VEGF/FGF-Src-MAPK and PI3K-P38 signalling pathways by gene expression analysis and a blocking assay with pathways-specific kinase inhibitors.Conclusions/SignificanceTaken together, our study demonstrated the more distinctive pro-angiogenic properties of 10 than other tanshinones and revealed 10 has potential for development as a pro-angiogenic agent for diseases associated with insufficient angiogenesis. Our results highlighted the great potential of adopting a newly modified one-pot approach to enhance the chemical diversity and biological activities of constituents from natural products regardless of their abundances.

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“…Therefore, it will be pivotal for the therapy of adenomyosis to inhibit cell migration and invasion. Previous studies have documented that TSIIA could inhibit cell migration and invasion in multiple cancer cells through regulating the expression of several wellknown invasion-and migration-associated molecules, such as matrix metalloproteinase (MMP) 2 and 9 [41][42][43]. Here, we showed that TSIIA significantly decreased the ability of cell migration and invasion in EESCs, and this effect was mediated by downregulation of 14-3-3f.…”

Section: Discussionmentioning

confidence: 52%

Tanshinone IIA inhibits the proliferation, migration and invasion of ectopic endometrial stromal cells of adenomyosis via 14-3-3ζ downregulation

Wan

Zou

Wan

et al. 2015

Arch Gynecol Obstet

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Anti-angiogenic effect of Tanshinone IIA involves inhibition of matrix invasion and modification of MMP-2/TIMP-2 secretion in vascular endothelial cells

Cited by 61 publications

References 28 publications

Tanshinone IIA induces intrinsic apoptosis in osteosarcoma cells both in vivo and in vitro associated with mitochondrial dysfunction

Tanshinone IIA induces intrinsic apoptosis in osteosarcoma cells both in vivo and in vitro associated with mitochondrial dysfunction

In Vivo Angiogenesis Screening and Mechanism of Action of Novel Tanshinone Derivatives Produced by One-Pot Combinatorial Modification of Natural Tanshinone Mixture from Salvia Miltiorrhiza

Tanshinone IIA inhibits the proliferation, migration and invasion of ectopic endometrial stromal cells of adenomyosis via 14-3-3ζ downregulation

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