Pre-clinical evaluation of kaempferide, a flavonoid from Chromolaena odorata, as a potential drug candidate against cervical cancer

Current chemotherapeutic regimens against breast cancer (BC) primarily target the receptor status of the breast tissue.Chemosensitization provides new insights to counter chemoresistance, a major obstacle that limits the benefits of chemotherapy of BC.By utilizing in vitro (Vinod et al., Cell Death and Disease, 2013) and two independent murine BC models; NSG mice bearing orthotropic triple-negative breast cancer (TNBC) xenografts (Haritha et al., 2021, Frontiers in Oncology) and Wistar rats bearing DMBA-induced breast tumors, we investigated the ability of curcumin in chemosensitizing BC, regardless of their receptor status, to 5-Fluorouracil (5-FU) chemotherapy.In both models, a significant synergistic antitumor potential was observed with a sub-optimal dose treatment of 5-FU plus curcumin, as evaluated by a reduction in the tumor-related parameters.We authenticated the pivotal role of thymidylate synthase (TS) in regulating the 5-FUcurcumin synergism using the TNBC pre-clinical model.Our study also confirmed the pharmacological safety of this combination using acute and chronic toxicity models.