of angiogenesis is VEGF. Various studies have shown it to be a potent stimulator of angiogenesis in vitro. Because of its critical role in angiogenesis, it has been targeted for controlling tumor progression. Limiting VEGF in tumors has been shown to lead to blood vessel destruction and to Pazopanib Armala prevent the growth of new ones, thus reducing the blood supply to the tumor. Inhibition of the VEGF tyrosine kinase signaling pathway blocked angiogenesis in growing tumors, leading to stasis and regression of the tumors. Thus, agents that can downregulate or inhibit the expression of VEGF or its signaling pathway in tumor cells could prove to be very promising in preventing tumor growth and metastasis. Saikosaponin C, one of the saikosaponins present in a Chinese herb, Radix bupleuri, has been found to have a potent inducing effect on human umbilical vein endothelial cells, viability and growth.
Saikosaponin C also induced endothelial cell migration and capillary tube formation. Saikosaponin C induced the gene expression or activation of MMP2, VEGF, and the p42/p44 MAPK that correlates with endothelial cell growth, migration, and angiogenesis, respectively. Dienogest Another study found that saikosaponins can inhibit the physiological angiogenesis of chicken embryos, especially for the medium and small vessels. CDDO Me and CDDO Im were shown to inhibit the activation of the ERK1/2 pathway after stimulation with VEGF in human umbilical vein endothelial cells. CDDO Me also potentiated the cytotoxic effects of TNF and chemotherapeutic agents.
This may be because CDDO Me inhibits NF κB through the inhibition of IκB kinase, leading to the suppression of NF κB regulated gene product expression and to angiogenesis. Boswellic acids Toxins 2010, 2 2449 suppressed VEGF induced phosphorylation of VEGF receptor 2 kinase with an IC50 of 1.68 M. Specifically, boswellic acids suppressed the downstream protein kinases of VEGFR2, including Src family kinase, focal adhesion kinase, ERK, AKT, mTOR, and ribosomal protein S6 kinase. In an ex vivo model, boswellic acids significantly inhibited blood vessel formation in the Matrigel plug assay in mice and effectively suppressed VEGF induced microvessel sprouting in a rat aortic ring assay. Furthermore, boswellic acids inhibited VEGF induced cell proliferation, chemotactic motility, and the formation of capillary like structures from primary cultured human umbilical vascular endothelial cells in a dose dependent manner.
Betulinic acid also inhibits growth factor induced in vitro angiogenesis by modulating mitochondrial function in endothelial cells. Various in vivo studies have found that celastrol can downregulate the density of tumor microvessels significantly at different doses. Immunohistochemistry showed that celastrol also decreased the levels of VEGFR1 and VEGFR2 expression, but not the level of VEGF expression. However, avicins, downregulate the expression of VEGF. An in vivo study showed that Ganoderma lucidum given at 100 and 200 mg/kg inhibited primary solid tumor growth in the spleen, liver metastasis, and secondary metastatic tumor growth in the liver in intrasplenic Lewis lung carcinoma implanted mice.
An in vivo assay system extract inhibited Matrigel induced angiogenesis. 5. Role of Triterpenoids in Cancer Treatment Triterpenoids are structurally diverse organic compounds. More than 20,000 triterpenoid varieties are formed by multiple modifications of the basic backbone structure. Several triterpenoids such as avicin, betulinic acid, boswellic acids, celastrol, diosgenin, madecassic acid, maslinic acid, momordin, saikosaponins, platycodon, pristimerin, ursolic acid, CDDO, and withanolide, have been shown in our laboratory and others to possess anticancer and anti inflammatory activities. Preliminary data from on