Flavonolignans: One Step Further in the Broad-Spectrum Approach of Cancer

Author(s): Diana S. Antal, Florina Ardelean, Stefana Avram, Ioana Z. Pavel, Corina Danciu*, Codruta Soica, Cristina Dehelean

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 20 , Issue 15 , 2020

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Graphical Abstract:


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: Proceeding from the presentation of natural flavonolignan subtypes and their occurrence, the present work reviews these compounds 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 presented.

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.

Keywords: Silybum flavonolignans, chemical structure, pro-apoptotic, anti-angiogenetic, iso-flavonolignans, nanoformulation.

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