南方医科大学学报2025，Vol.45Issue(7)：1460-1470,11.DOI:10.12122/j.issn.1673-4254.2025.07.12
雷氏大疣蛛多肽毒素组分通过激活促凋亡通路和协同作用抑制癌细胞增殖
The peptide toxin components and nucleotide metabolites in Macrothele raveni venom synergistically inhibit cancer cell proliferation by activating the pro-apoptotic pathways
摘要
Abstract
Objective To evaluate the inhibitory effect of Macrothele raveni crude venom against proliferation of different cancer cells and identify the active components in the venom.Methods Different cancer cell lines were treated with different concentrations of Macrothele raveni venom for 48 h,and cell proliferation and the half-maximal inhibitory concentrations(IC50)of the venom were assessed with CCK-8 assay.The apoptosis rate of breast cancer MCF7 cells following the treatment was analyzed with flow cytometry,and the changes in cellular caspase-8 and caspase-9 expressions were detected.The crude venom was separated into protein,peptide,and small-molecule compound fractions using gel filtration chromatography and high-performance liquid chromatography(HPLC).The protein and peptide components were identified using proteomics analysis,and small-molecule compounds were structurally characterized using nuclear magnetic resonance(NMR),mass spectrometry(MS),and HPLC.Results 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 via 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 Macrothele gigas 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.Conclusion The inhibitory effects of Macrothele raveni venom,which vary significantly across different cancer cell lines,are attributed primarily to its peptide components,which may act synergistically with the nucleotide metabolites.关键词
雷氏大疣蛛/多肽毒素/癌细胞/抗增殖作用Key words
Macrothele raveni/peptide toxins/cancer cells/anti-proliferation引用本文复制引用
谢婷,王云云,郭婷,袁春华..雷氏大疣蛛多肽毒素组分通过激活促凋亡通路和协同作用抑制癌细胞增殖[J].南方医科大学学报,2025,45(7):1460-1470,11.基金项目
国家重点研发计划(2023YFC3504304)Supported by National Key Research and Development Program of China(2023YFC3504304). （2023YFC3504304）
