Abstract
BackgroundAngiogenesis is one of cancer hallmarks that are required for both cancer progression and metastasis. In this study we examined the antiangiogenic properties of the ethanolic crude extracts of four Salvia species grown in Jordan.MethodsThe direct antiangiogenic activity was evaluated using various models: ex vivo rat aortic ring assay, in vitro assessment of HUVEC proliferation and migration, and in vivo CAM assay, while we used the changes in the expression of HIF-1α and VEGF in breast cancer cells (MCF 7) as an indicative for the indirect antiangiogenic activity.ResultsAll four crude extracts showed a potential antiangiogenic activity in the rat aortic assay, however two species were found to be cytotoxic against Fibroblast cell line (PLF); the finding that caused the exclusion of these two extracts from further studies. Of the two remaining extracts, S. triloba showed very promising direct and indirect antiangiogenic activities. S. triloba inhibited the HUVEC proliferation with an IC50 of 90 μg/mL and HUVEC migration by 82% at 150 μg/mL. Furthermore, the in vivo CAM assay also illustrated the high impact of S. triloba against the newly formed vessel in the chicken embryonic membrane. Interestingly, the S. triloba inhibited the expression of VEGF at the mRNA and protein and the HIF-1α mRNA in the MCF 7 breast cancer cells under both normoxic and hypoxic conditions.ConclusionsTaken together, all these findings of the direct and indirect angiogenic investigations nominated S. triloba as a highly potent antiangiogenic plant that may have chemotherapeutic and/or chemoprevention potentials.
Highlights
Angiogenesis is one of cancer hallmarks that are required for both cancer progression and metastasis
Rat aortic ring assay In order to evaluate the antiangiogenic properties of the plant extracts, we performed the rat aortic ring assay at two concentrations: 50 and 100 μg/mL (Figure 1)
S. hormium failed to keep any inhibitory activity at this concentration (P > 0.05) (Table 1 and Figure 1)
Summary
Angiogenesis is one of cancer hallmarks that are required for both cancer progression and metastasis. Angiogenesis is the formation of new blood vessels. Cancer is angiogenesis dependent; any significant increment in tumour size must be in synchrony with increment in the blood supply. The new blood vessels supply the tumour cells with extra amount of oxygen and nutrients, and most importantly they facilitate cancer cell metastasis to other localities [1]. Breast cancer is the most common cancer in women counting for approximately 27% of all new cancers [3]. It is characterized by a distinct metastatic pattern [4]
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