Background: The small chemical class of flavonolignans encompasses unique hybrid molecules with
versatile biological activities. Their anticancer effects have received considerable attention, and a large body of
supporting evidence has accumulated. Moreover, their ability to interact with proteins involved in drug resistance,
and to enhance the effects of conventional chemotherapeutics in decreasing cell viability make them
influential partners in addressing cancer.
Objective: The review provides an outline of the various ways in which flavonolignans advance the combat
against cancer. While the main focus falls on flavonolignans from milk thistle, attention is drawn to the yet,
underexplored potential of less known flavonolignan subgroups derived from isoflavonoids and aurones.
Methods: The present work reviews proceedings from the presentation of natural flavonolignan subtypes and
their occurrence with regard to their molecular targets in cancer, anti-angiogenetic effects, synergistic efficacy in
conjunction with anticancer agents, reversal of drug resistance, and importance in overcoming the side effects of
anticancer therapy. Recent advances in the endeavor to improve flavonolignan bioavailability in cancer are also
Conclusions: Significant progress has been achieved in detailing the molecular mechanisms of silybin and its
congeners in experimental models of cancer. The availability of novel formulations with improved bioavailability,
and data from phase I clinical trials in cancer patients provide an encouraging basis for more extensive trials
aimed at evaluating the benefits of Silybum flavonolignans in cancer management. On the other hand, further research
on the antitumor efficacy of iso-flavonolignans and other subtypes of flavonolignans should be pursued.