LAUSR

Simple Summary Flavonoids are plant polyphenolic secondary metabolites, commonly consumed in the human diet. Lensoside Aβ is a quercetin glycoside isolated from the aerial parts of lentil (Lens culinaris) organs. The activity of this secondary metabolite, especially in terms of its anticancer potential, has been poorly studied. Currently, there are no published data about the effect of this flavonoid on gliomas, which are so-far incurable, aggressive neoplasms of the central nervous system with a highly infiltrative character. In this study, we found that lensoside Aβ itself exhibits poor anti-glioma properties but exerts a strongly potentiated effect in combination with sorafenib (inhibitor of Raf kinase) on apoptosis induction in cancer cells. Our results have shown that sorafenib with lensoside Aβ seems to be a promising combination that might be useful in glioma therapy. Additionally, the former observation, pointing to the key role of flavonoids as adjuvants in chemotherapy, is confirmed. Abstract Aim: The anti-glioma effect of lensoside Aβ alone and in combination with sorafenib (pro-survival Raf kinase inhibitor) was evaluated for the first time in terms of programmed cell death induction in anaplastic astrocytoma and glioblastoma multiforme cell lines as an experimental model. Apoptosis, autophagy, and necrosis were identified microscopically (fluorescence and scanning microscopes) and confirmed by flow cytometry (mitochondrial membrane potential MMP and cell death). The expression of apoptotic (caspase 3) and autophagic markers (beclin 1) as well as Raf kinase were estimated by immunoblotting. The FTIR method was used to determine the interaction of the studied drugs with lipid and protein groups within cells, while the modes of drug action within the cells were assessed with the FLIM technique. Results: Lensoside Aβ itself does not exhibit anti-glioma activity but significantly enhances the anti-cancer potential of sorafenib, initiating mainly apoptosis of up to 90% of cells. It was correlated with an increased level of active caspase 3, a reduced MMP value, and a lower level of Raf kinase. The interaction with membrane structures led to morphological changes typical of programmed death. Conclusions: Our results indicate that lensoside Aβ plays an important role as an adjuvant in chemotherapy with sorafenib and may be a potential candidate in anti-glioma combination therapy.