α ‐Conopeptide From Conus planorbis Inhibits Glioblastoma Stem Cells and Angiogenesis via Sonic Hedgehog and ADAMDEC1–FGF2–FGFR1 Loop Signaling Pathway

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor with limited effective treatments. This study explores the anti‐GBM potential of an α ‐conopeptide isolated from the venom of Conus planorbis , a marine cone snail from Rameswaram, India. Peptide extraction and BCA assay quantified an average concentration of 473.34 ± 70.07 µg/mL. Structural analysis via 1 H nuclear magnetic resonance (NMR) revealed a stable tertiary structure with aromatic, aliphatic, sulfur‐containing, and basic amino acids, stabilized by hydrogen bonds and disulfide bridges. Molecular docking showed strong interactions between the α ‐conopeptide and GBM‐related proteins PTCH1, FGFR1, and fibroblast growth factor 2 (FGF2), suggesting inhibition of sonic hedgehog (SHH) and ADAM‐like Decysin 1 (ADAMDEC1)–FGF2–FGFR1 loop signaling pathway. Molecular dynamics simulations confirmed stable binding with FGFR1. In vitro assays using U87 GBM cells demonstrated that the α ‐conopeptide had greater cytotoxicity (IC 50 ≈ 250 µg/mL) than temozolomide (IC 50 ≈ 320 µg/mL). Additional chorioallantoic membrane (CAM) and brine shrimp lethality tests supported its potent bioactivity, with a lower LD 50 (50.24 µg/mL) compared to temozolomide (125.82 µg/mL). These findings indicate that the α ‐conopeptide from C. planorbis possesses multi‐target anticancer activity targeting via SHH and FGFR1 loop signaling pathway, structural stability, and superior cytotoxic potency against GBM, highlighting its potential as a novel marine‐derived therapeutic agent.