Evaluation of anti-invasive and anti-migratory effects of kaempferol and docetaxel co-treatment via modulation of drug metabolising enzymes in 2D and 3Dbreast cancer models.

Docetaxel is a key chemotherapeutic agent for treating locally advanced or metastatic breast cancer, but its effectiveness is often hindered by metabolic inactivation from drug-metabolizing enzymes, leading to multidrug resistance (MDR). This study aims to investigate the anti-metastatic effects of combining kaempferol, a flavonoid known for its anticancer properties, with docetaxel in both 2D and 3D breast cancer models. It will explore the potential drug-drug interactions and physiological toxicity through in silico studies, alongside in vitro assessments of how the combination affects CYP450 enzymes. Cytotoxic effects of kaempferol, docetaxel, and their combination will be evaluated using viability assays and the effect of the combination will further be analyzed using Combenefit and CompuSyn software. The research will also assess how this combination impacts hepatic clearance, metabolism, and efflux of docetaxel using liver models (S9 fractions and human liver micrrosomes) and Multidrug resistance kits. The effect of the combination on metastatic processes in breast cancer models will be assessed using cell migration and invasion assays. In conclusion, the study aims to clarify the mechanisms behind kaempferol’s effects and its combination with docetaxel in combating breast cancer, and effect of kaempferol on the metabolic inactivation of docetaxel.

Faculty Supervisor:

Juliet Daniel

Student:

Partner:

University of Limpopo

Discipline:

Life Sciences

Sector:

Health and Related Sciences & Technology

University:

McMaster University

Program: