| In vitro: |
| Pharm Biol. 2013 Aug;51(8):1061-5. | | Anti-angiogenic activity of salvicine.[Pubmed: 23750780] | Salvicine is a pharmacologically active derivative from Chinese medicinal plant Salvia prionitis Hance (Labiatae). It has been reported that Salvicine inactivates β1 integrin and inhibits integrin-mediated cell adhesion to fibronectin. Given the emerging correlation between integrins and angiogenesis, we propose that Salvicine abolishes cell adhesion and subsequent metastasis by inhibiting angiogenisis. The anti-angiogenesis activities of Salvicine were investigated for the first time.
METHODS AND RESULTS:
The cytotoxicity of Salvicine on human microvascular endothelial cells (HMECs) and non-small cell lung adenocarcinoma A549 cells were measured at doses between 0.625 and 200 µM. Changes of cell migration were detected with doses of Salvicine at 1.25-5 µM, and basement membrane matrigel matrix was used for the assessment of tube formation at concentrations ranging from 0.078 to 1.25 µM. In addition, mRNA expression of basic fibroblast growth factor (bFGF) in A549 cells was studied with the RT-PCR assay. In vitro studies revealed that the IC50 of Salvicine on A549 cells (18.66 µM) was two-fold higher than that of HMECs (7.91 µM). Salvicine (1.25, 2.5 and 5.0 μM) inhibited significantly the endothelial cell migration up to 56, 73 and 82%, respectively. Salvicine decreased capillary-like tube formation of HMECs with high potency. Furthermore, it (30 µM) markedly reduced the mRNA expression of bFGF in A549 cells, while vascular endothelial growth factor (VEGF) mRNA expression remained unchanged.
CONCLUSIONS:
Our results suggest that Salvicine has potent anti-angiogenic activity through the inhibition on the sequential angiogenic cascades: proliferation, migration and tube formation and is associated with influence on the expression of bFGF of tumor cell. | | Biochem Pharmacol. 2001 Sep 15;62(6):733-41. | | Salvicine, a novel DNA topoisomerase II inhibitor, exerting its effects by trapping enzyme-DNA cleavage complexes.[Pubmed: 11551518] | Salvicine, a structurally modified diterpenoid quinone derived from Salvia prionitis, is a novel anticancer drug candidate. The compound has significant in vitro and in vivo activity against malignant tumor cells and xenografts, especially some human solid tumor models. This anticancer activity of Salvicine is associated with its ability to induce tumor cell apoptosis.
METHODS AND RESULTS:
Salvicine was also found to have a profound cytotoxic effect on multidrug-resistant (MDR) cell lines by down-regulating the expression of MDR-1 mRNA of MDR cells. Salvicine acted as a topoisomerase II (Topo II) poison through its marked enhancement effect on Topo II-mediated DNA double-strand breaks as observed in the DNA cleavage assay. Strong inhibitory activity of Salvicine against Topo II was observed in a kDNA decatenation assay, with an approximate IC(50) value of 3 microM. A similar result was obtained by a Topo II-mediated supercoiled DNA relaxation assay. In contrast, no inhibitory activity was observed against the catalytic activity of Topo I. When the effects of Salvicine on individual steps of the catalytic cycle of Topo II were dissected, it was found that the mechanism by which Salvicine inactivates Topo II is different from that by other anti-Topo II agents. Salvicine greatly promoted Topo II-DNA binding and inhibited pre- and post-strand Topo II-mediated DNA religation without interference with the forward cleavage steps. In addition, Salvicine was not a DNA intercalative agent, as demonstrated by DNA unwinding assays.
CONCLUSIONS:
The results of this study indicate that the inhibitory activity of Salvicine against Topo II was derived from its ability to stabilize DNA strand breaks through interactions with the enzyme alone or with the DNA-enzyme complex. It is therefore postulated that Salvicine acts on Topo by trapping the DNA-Topo II complex, which in turn produces anticancer effects. |
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