Abstract

Background: Besides the numerous biologic and pharmacologic functions in the human body that act as potent antioxidants, flavonoids (flavones, flavanones, flavonols, flavanols and isoflavones) are noted as cancer preventive or therapeutic agents.

Methods: This review summarizes the published data using PubMed, Science Direct, and Scopus.

Results: In this context, recognition and introduction of the most active cytotoxic flavonoids as promising agents for cancer therapy gives insight for further evaluations. However, there are some critical points that may affect the entering of flavonoids as active cytotoxic phytochemicals in the clinical phase. Issues such as the abundance of active species in nature, the methods of extraction and purification, solubility, pharmacokinetic profile, presence of the chiral moieties, method of synthesis, and structure modification may limit the entry of a selected compound for use in humans. Although plenty of basic evidence exists for cytotoxic/antitumor activity of the versatility of flavonoids for entry into clinical trials, the above-mentioned concerns must be considered.

Conclusion: This review is an effort to introduce cytotoxic natural flavonoids (IC50< 10 µM) that may have the potential to be used against various tumor cells. Also, active constituents, molecular mechanisms, and related clinical trials have been discussed as well as the limitations and challenges of using flavonoids in clinic.

Keywords: Flavonoids, potent cytotoxic, molecular mechanism, clinical trial, limitations, potent antioxidants.