Background: Besides numerous biological and pharmacological function in the body as potent antioxidants,
flavonoids (flavones, flavanones, flavonols, flavanols and isoflavones) are noted as cancer preventive or
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 help to give insight into further evaluations. However, there are some critical points which may
affect the entering of flavonoids as active cytotoxic phytochemicals in clinical phase. Issues such as abundance of
active species in the 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 human. Although there may present a lot of basic evidence for cytotoxic/antitumor activity of
versatility of flavonoids for the entry to clinical trials, the above-mentioned concerns must be considered.
Conclusion: This review is an effort to introduce the cytotoxic natural flavonoids (IC50< 10 μM) which may have
the potential to be used against various tumor cells. Also, active constituents, molecular mechanisms and the
related clinical trials are discussed. At the end, the limitations and challenges of using flavonoids in clinic were