Methoxy-Substituted γ-Oxa-ε-Lactones Derived from Flavanones-Comparison of Their Anti-Tumor Activity In Vitro

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-10, Vol.26 (20), p.6295
• Main Authors: Pawlak, Aleksandra, Henklewska, Marta, Hernández-Suárez, Beatriz, Siepka, Monika, Gładkowski, Witold, Wawrzeńczyk, Czesław, Motykiewicz-Pers, Karolina, Obmińska-Mrukowicz, Bożena
• Format: Article
• Language: English
• Subjects: Animals; Annexin V; anti-cancer activity; Antineoplastic Agents - pharmacology; Antitumor activity; Apoptosis; Apoptosis - drug effects; Aromatic compounds; Biological activity; Cancer therapies; Cell Line, Tumor; Cell Survival - drug effects; Cytotoxicity; Dogs; Drug Screening Assays, Antitumor - methods; flavanone-derived lactones; flavanones; Flavanones - chemistry; Flavonoids; Glucocorticoids; In Vitro Techniques; Iodides; Lactones; Lactones - chemistry; Lactones - pharmacology; Leukemia; Leukemia - drug therapy; Leukemia - metabolism; Leukemia - pathology; Lymphoma; Lymphoma - drug therapy; Lymphoma - metabolism; Lymphoma - pathology; Molecular Structure; Propidium iodide; Structure-Activity Relationship; Substitutes; Tumor cell lines; Tumors
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26206295

The study investigated four flavanone-derived γ-oxa-ε-lactones: a parent unsubstituted compound and its three derivatives with the methoxy group in positions 2', 4' and 8. Our objective was to find out if the introduction of the methoxy group into the aromatic ring affects in vitro anti-tumor potency of the investigated lactones. Cytotoxic and pro-apoptotic effects were assessed with cytometric tests with propidium iodide, annexin V, and Western blot techniques. We also investigated potential synergistic potency of the tested lactones and glucocorticoids in canine lymphoma/leukemia cell lines. The tested flavanone-derived lactones showed anti-cancer activity in vitro. Depending on its location, the methoxy group either increased or decreased cytotoxicity of the derivatives as compared with the parent compound. The most potent lactone was the one with the methoxy group at position 4' of the B ring (compound ), and the weakest activity was observed when the group was located at C-8 in the A ring. A combination of the lactones with glucocorticoids confirmed their synergy in anti-tumor activity in vitro. Methoxy-substituted flavanone-derived lactones effectively kill canine lymphoma/leukemia cells in vitro and, thanks to their synergistic action with glucocorticoids, may potentially be applied in the treatment of hematopoietic cancers.