Dual Antitumor Effects of Solanum incanum L. in Lung and ColonicAdenocarcinomas via TRAIL-Mediated Extrinsic Apoptotic Pathway:A Network Pharmacology and Multi-Omics Investigation

Background:: Solanum incanum L. (S. incanum) is a Traditional Chinese Medicine (TCM) known for its heat-clearing and detoxifying properties. This study evaluates the anti-cancer potential of S. incanum in lung and colorectal adenocarcinoma. Also, we aim to confirm the connection between the lung and the large intestine, as proposed in TCM theory. Methods:: This study employed network pharmacology analysis, MTT and morphological analysis, Western blotting, and molecular docking to investigate the anti-cancer effects of S. incanum, particularly through its activation of the TRAIL-mediated extrinsic apoptotic pathway. Results:: This study identified 15 active compounds in S. incanum, with glycosylated alkaloids such as α-solanine and solasonine highlighted as key bioactive compounds. KEGG and GO analyses revealed that S. incanum influences apoptosis-related pathways, particularly the extrinsic apoptotic pathway, regulating mediators such as CASP3, CASP8, and various TNF- related receptors. The anticancer potential was assessed through cellular studies using A549 and HT29 cell lines, with MTT cell viability assays showing that α-solanine induces apoptosis, with IC50 values between 20 and 30 μM. Western blot analysis demonstrated that S. incanum activates apoptosis via the TRAIL-mediated extrinsic apoptotic pathway, promoting CASP8, CASP3, and PARP1 cleavage in a dose-dependent manner, affecting DNA synthesis. Molecular docking further identified α-solanine and solasonine as compounds that bind to critical proteins in the TRAIL-related apoptotic pathway, confirming their roles in promoting apoptosis. Discussion:: The shared activation of the TRAIL-mediated apoptotic pathway in both lung and colorectal adenocarcinoma models suggests a common molecular mechanism. These findings provide experimental evidence linking traditional ethnopharmacological concepts with apoptosis-related anti-cancer activity Conclusions:: This study emphasizes that the main compound of S. incanum, α-solanine, supports the ethnopharmacological concept of “Exterior-interior Pairing of the Lung and Large Intestine”, thereby demonstrating that both lung and colorectal adenocarcinomas share a common anticancer pathway through a TRAIL-related apoptotic mechanism.