Targeting Oncogenic STAT3 Pathways in Osteosarcoma With Serratia marcescens Peptides

Signal transducer and activator of transcription 3 (STAT3) is emerging as a pivotal oncogenic factor and its overexpression has been associated to osteosarcoma (OS) development, progression, and poor prognosis. It may be a promising therapeutic target for OS treatment. Constitutive activation of STAT3 facilitates tumorigenesis by inducing aberrant cell growth, apoptosis evasion, immune suppression, and increased angiogenesis. In this study, we screened a panel of bacterial peptides from Serratia marcescens , namely, prodigiosin, serralysin, chitinase B, chitinase C, and L‐methioninase, for their capability to inhibit the STAT3 activity. In silico pipeline was used to predict the anticancer potential of each candidate peptide, alongside its physicochemical properties and predicted toxicity and allergenic. The three‐dimensional structures of each peptide were modeled through PEP‐FOLD and validated via Ramachandran plot analysis with */PROCHECK. The estimation of binding strength and stability of the ensuing complexes was done by molecular docking with HADDOCK, followed by molecular dynamics simulations. The interactions were confirmed by binding free‐energy analyses. The peptides showed strong and stable binding to the active domain of STAT3, along with favorable pharmacokinetic predictions. These findings indicate that the selected S. marcescens peptides may act as promising candidates for further development in peptide‐based therapeutics against OS.