Antiproliferative Activity of Buddleja saligna (Willd.) against Melanoma and In Vivo Modulation of Angiogenesis

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 mu 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 mu g/mL (DT-BS-01). BS (30 mu g/mL) significantly inhibited interleukin (IL)-6 (83.26 +/- 17.60%) and IL-8 (100 +/- 0.2%) production, whereas DT-BS-01 (5 mu 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 mu 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.

Automated summary

Melanoma cells secrete pro-angiogenic factors which play a key role in growth, proliferation, and metastasis. In this study, Buddleja saligna and a triterpenoid mixture were found to inhibit the growth of melanoma cells with minimal effects on normal cells. Additionally, these compounds showed inhibitory effects on vascular endothelial growth factor and interleukins, as well as reducing new blood vessel formation.