Synergistic combination of doxorubicin with fisetin for the treatment of lymphoma

Abstract

Lymphoma is a common cancer of the lymphatic system, and its treatment presents considerable clinical difficulties due to the constraints of existing medicines. Anticancer drug such as Doxorubicin (DOX) is an effective chemotherapeutic drug that is frequently used to treat lymphoma and other cancers; however, it is linked with considerable toxicities. Fisetin, a naturally occurring flavonoid, exhibits anticancer properties and has the potential to augment the therapeutic effects of DOX. This study explores the synergistic effects of combining DOX with fisetin in the treatment of lymphoma. The combination of DOX and fisetin significantly inhibits cell viability, induced membrane blabbing, chromatin condensation, and promoted apoptosis compared to monotherapies. The study also showed that the synergistic effect of fisetin along with DOX significantly promotes apoptosis in DL cells through intracellular ROS generation, mitochondrial aggregation at the periphery of the nucleus and, increased p53, Bax, cytochrome c, caspase 3, caspase 9, and cleaved caspase 9 expression. Additionally, combination therapy not only increased the mean survival of the treated group animals but also reduced the tumor burden. While histopathological parameters have shown overall improvement in combination therapy. This study proposes a novel combinational therapy for the treatment of lymphoma and requires further clinical investigation.