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.
Description:
SUPPLEMENTARY MATERIAL : FIGURE S1: Representative (a) 1H-NMR (Methanold4, 400 MHz) and (b) 13C-NMR (Methanol-d4, 100 MHz) spectra of DT-BS-01; FIGURE S2: Extracted-ion chromatogram (XIC) of m/z 455.35 in negative ionization mode of LC-MS analysis of (a) DT-BS-01 (b) Oleanolic acid and (c) Ursolic acid; FIGURE S3: Extracted-ion chromatogram (XIC) of m/z 479.35 in positive ionization mode of LC-MS analysis of (a) DT-BS-01 (b) Oleanolic acid and (c) Ursolic acid; FIGURE S4: Negative ionization mode mass spectra of (a) DT-BS-01 (b) Oleanolic acid and (c) Ursolic acid; FIGURE S5: Positive ionization mode mass spectra of (a) DT-BS-01 (b) Oleanolic acid and (c) Ursolic acid; FIGURE S6: Synthesis process of nanoparticles using Buddleja saligna; FIGURE S7: Characterization of BS-AuNPs. (a) UV-Vis absorption spectra. (b) In vitro stability in buffer solutions after 24 h. (c) In vitro stability in buffer solutions after 48 h. (d) Transmission electron micrograph. (e) Particle size distribution; FIGURE S8: Characterization of BS-AgNPs. (a) UV-Vis absorption spectra. (b) In vitro stability in buffer solutions after 24 h. (c) In vitro stability in buffer solutions after 48 h. (d) Transmission electron micrograph. (e) Particle size distribution; FIGURE S9: Characterization of BS-PdNPs. (a) UV-Vis absorption spectra. (b) Transmission electron micrograph. (c) Particle size distribution (d) In vitro stability in buffer solutions after 24 h. (e) In vitro stability in buffer solutions after 48 h.