The Flavonoid Quercetin Protects MDCK Cells against Toxicity of CPT by Induction of Autophagy

In chemotherapy, two or more pharmaceuticals targeting different metabolic pathways are often combined in the expectation that they will synergize or function additively against the tumor. Flavonoids, typically polycyclic plant pigments, have many beneficial effects in humans, including being putatively anticancer, inducing apoptosis by undefined means. Camptothecin (CPT), a powerful chemotherapeutic natural product used in Chinese traditional medicine is a topoisomerase inhibitor. In this study, we investigated whether two recommended flavonoids from plants, baicalein and quercetin, affected the capability of CPT to kill cells. We exposed MDCK (Madin Darby Canine Kidneys) cells to each flavonoid in the presence or absence of CPT; the flavonoids themselves were very modestly toxic at 50-100 μg/ml. However, quercetin but not baicalein reduces cell death induced by CPT. The flavonoids induced autophagy, which can protect cells against CPT and other stressors and is likely to be a major factor protecting cells from toxins like CPT. This potential effect indicates that not all putatively pro-apoptotic agents will synergize with others, and they may even restrain the oncolytic toxicity of other chemotherapeutic drugs. Presumptively beneficial natural products used in folk medicine may even antagonize the oncolytic effect of the chemotherapy.