Cytotoxic Potential and Metabolomic Profiling of Solanum lycopersicum Roots Extract and Their Nanocrystals: An In Silico Approach.

Solanum lycopersicum L. Moench (Tomato) is a rich source of bioactive compounds. This study investigated the anticancer potential of S. lycopersicum roots methanol extract (TMESLR) and their nanocrystals (TMESLR-NCs) against breast (MCF-7), hepatocellular (HepG2), and colon (Caco-2) cancer cell lines, for the first time. TMESLR exhibited significant cytotoxicity against all 3 cell lines, with the nanocrystals demonstrating enhanced activity, Caco-2, MCF-7, and HepG2 cells with IC50 values of 9.69 ± 0.6, 12.52 ± 0.58, and 14.34 ± 0.62 µg/mL, respectively. Whereas, the prepared TMESLR-NCs displayed significantly the highest cytostatic potential against Caco-2 with IC50 value of 5.733 ± 0.29 µg/mL. Metabolomic profiling revealed 17 secondary metabolites, including flavonoids, phenolic acids, and terpenoids. In silico analyses, including PPI network construction, GO enrichment, and KEGG pathway analysis, highlighted the involvement of apoptotic pathways, p53 signaling, and TNF signaling in the anticancer effects of TMESLR. Molecular docking studies identified chlorogenic acid and inosine as potential inhibitors of Histone Deacetylase 2 (HDAC2). Inosine (6) displayed a superior docking score of -7.86 kcal/mol, interacting with critical residues GLY154, ASP269, and HIS146. On the other hand, chlorogenic acid (12) achieved a docking score of -7.32 kcal/mol, forming stable interactions with TYR308, PHE210, and LEU276 residues. These findings suggest that TMESLR and TMESLR-NCs possess promising anticancer activity and warrant further investigation as potential therapeutic agents.