[The peptide toxin components and nucleotide metabolites in <i>Macrothele raveni</i> venom synergistically inhibit cancer cell proliferation by activating the pro-apoptotic pathways].

The crude venom exhibited strong concentration-dependent inhibitory effects on proliferation of MCF7 cells and nasopharyngeal carcinoma SUNE1 and HONE1 cells (IC₅₀ of 2.14±0.29, 1.57±0.14, and 2.85±0.15 µg/mL, respectively), with less potent inhibitory effects in gastric cancer HGC27 cells and colorectal cancer SW620 cells (IC₅₀ of 3.02±0.27 and 3.02±0.28 µg/mL, respectively). The crude venom significantly promoted MCF7 cell apoptosis likely <i>via</i> the caspase 8 signaling pathway. The protein fraction from the crude venom showed a weak inhibitory effect in MCF7 cells, whereas the peptide fraction exhibited a much stronger inhibitory effect (IC₅₀ of 6.41±0.31 µg/mL). The peptides in the peptide fraction, with relative molecular mass around 10 000, were homologous to those found in <i>Macrothele gigas</i> venom. The small-molecule fraction consisted mainly of nucleotide metabolites without obvious inhibitory effects in MCF7 cells, but its combination with the peptide fraction showed significantly enhanced inhibitory activity. C<b>onclusion</b> The inhibitory effects of <i>Macrothele raveni</i> venom, which vary significantly across different cancer cell lines, are attributed primarily to its peptide components, which may act synergistically with the nucleotide metabolites.