Pharmacodynamics and safety in relation to dose and response of plant flavonoids in treatment of cancers

Despite the recent advancements in developing bioactive nutraceuticals as anticancer modalities, their pharmacodynamics, safety profiles, and tolerability remain elusive, limiting their success in clinical trials. The failure of anticancer drugs in clinical trials can be attributed to the changes in drug clearance, absorption, and cellular responses, which alter the dose-response efficacy, causing adverse health effects. Flavonoids demonstrate a biphasic dose-response phenomenon exerting a stimulatory or inhibitory effect and often follow a U-shaped curve in different preclinical cancer models. A double-edged sword, bioflavonoids' antioxidant or prooxidant properties contribute to their hormetic behavior and facilitate redox homeostasis by regulating the levels of reactive oxygen species (ROS) in cells. Emerging reports suggest a need to discuss the pharmacodynamic broad-spectrum of plant flavonoids to improve their therapeutic efficacy, primarily to determine the ideal dose for treating cancer. This review discusses the dose-response effects of a few common plant flavonoids against some types of cancers and assesses their safety and tolerability when administered to patients. Moreover, we have emphasized the role of dietary-rich plant flavonoids as nutraceuticals in cancer treatment and prevention.