Investigating the anti-cancer effects of α-solanine on glioblastoma cell-lines for in-vitro evaluation against the chemotherapeutic standard-of-care

Abstract

Despite optimal treatment, glioblastoma multiforme (GBM) has an abysmal associated prognosis of approximately 15 months. Published literature has increasingly demonstrated the potential of phytochemicals as putative agents against cancer. α-solanine, a glycoalkaloid derived from plants belonging to the genus Solanum, has emerged as a promising anti-cancer molecule. Here, the efficacy of α-solanine versus temozolomide (TMZ) against U87MG, U251 and T98G GBM cell lines in-vitro was investigated. Viability, migration, and invasion assays were conducted to assess α-solanine’s anti-cancer potential in comparison to TMZ. Moreover, the effect of α-solanine on cell death was investigated on a cellular level through fluorescent imaging and flow cytometry, and on a molecular level through rt-PCR and proteome profiling assays. The GBM cell lines used in the study were confirmed to be IDHwildtype according to the WHO 2021 CNST classification. α-solanine induced potent cytotoxic on all GBM lines, with IC50 ranging between 19.66 µM – 22.87 µM, while also demonstrating significantly inhibiting GBM cell migration, in comparison to TMZ treatment. Fluorescent imaging and flow-cytometry demonstrated increased occurrence of autophagic cell death, however this finding was not statistically different between α-solanine and control treatments. Rt-qPCR and anti-body array profiling demonstrated upregulation of both apoptotic and autophagy proteins. The upregulation of BECN1 at both RNA and protein levels suggests its key role in α-solanine-induced cell death. Additionally, α-solanine may be an inducer of mitophagy through the upregulation of BNIP3L. Further investigations are required to consolidate α-solanine's effects on GBM cells, and the specific mechanisms of cell death it induces. Results presented in this study contribute to the search for novel and effective treatments for GBM. Further work should strive to increase the number biological replicates for the experiments conducted to and carry out alternative methods to strengthen this study’s findings. Moreover, in-vivo experiments and testing using patient-derived GBM tissue to better evaluate the clinical potential of α-solanine.