Solanum glycoalkaloid solamargine inhibits growth of pediatric high-grade glioma cells under normoxia and hypoxia conditions

Pediatric high-grade gliomas remain a significant therapeutic challenge due to their resistance to conventional treatments. The aim of this study was to investigate the cytotoxic potential of solamargine (SM), a natural glycoalkaloid, alone and in combination with the chemotherapeutic agent temozolomide (TMZ) against the human KNS-42 glioma cell line. Solamargine significantly reduced cell viability and proliferation in a concentration-, time-, and hypoxia-dependent manner, while selectively sparing non-tumor human astrocytes (NHA). Morphological changes indicative of cell stress and death were observed, although SM did not markedly impair the migratory capacity of KNS-42 cells. In contrast, TMZ exhibited limited cytotoxicity against KNS-42 cells but demonstrated off-target effects on NHA cells. Combination therapy resulted in significant antagonism, with TMZ diminishing the cytotoxic effects of SM. These findings indicate the potential of SM to serve as a selective therapeutic agent for gliomas. Data obtained emphasize (1) the need for further research to optimize combination strategies and (2) to elucidate the underlying mechanisms of drug interactions.