Antiproliferative activity of Buddleja saligna (willd.) against melanoma and in vivo modulation of angiogenesis

Abstract

Melanoma cells secrete pro-angiogenic factors, which stimulates growth, proliferation and metastasis, and therefore are key therapeutic targets. Buddleja saligna (BS), and an isolated triterpenoid mixture (DT-BS-01) showed a fifty percent inhibitory concentration (IC50) of 33.80 1.02 and 5.45 0.19 g/mL, respectively, against melanoma cells (UCT-MEL-1) with selectivity index (SI) values of 1.64 and 5.06 compared to keratinocytes (HaCat). Cyclooxygenase-2 (COX-2) inhibition was observed with IC50 values of 35.06 2.96 (BS) and 26.40 4.19 g/mL (DT-BS-01). BS (30 g/mL) significantly inhibited interleukin (IL)-6 (83.26 17.60%) and IL-8 (100 0.2%) production, whereas DT-BS-01 (5 g/mL) showed 51.07 2.83 (IL-6) and 0 6.7% (IL-8) inhibition. Significant vascular endothelial growth factor (VEGF) inhibition, by 15.84 4.54 and 12.21 3.48%, respectively, was observed. In the ex ovo chick embryo yolk sac membrane assay (YSM), BS (15 g/egg) significantly reduced new blood vessel formation, with 53.34 11.64% newly formed vessels. Silver and palladium BS nanoparticles displayed noteworthy SI values. This is the first report on the significant anti-angiogenic activity of BS and DT-BS-01 and should be considered for preclinical trials as there are currently no US Food and Drug Administration (FDA) approved drugs to inhibit angiogenesis in melanoma.