A review of biologically active flavonoids as inducers of autophagy and apoptosis in neoplastic cells and as cytoprotective agents in non-neoplastic cells

Abstract

Phytochemicals are a diverse group of compounds found in various fruits, vegetables, nuts, and legumes. Many phytochemicals have been observed to possess health benefits. Some have been found to be chemoprotective or can act as chemotherapeutics by inducing autophagy, apoptosis, or otherwise regulating the cell cycle. Many also act as potent antioxidants. Flavonoids are a subclass of bioactive phytochemicals consisting of two phenolic benzene rings, joined together by a heterocyclic pyran or pyrone. It has been observed in multiple studies that there is a correlation between diets rich in flavonoids and a reduction in cancer levels, heart disease, neurodegenerative diseases, and other pathologies. As foods containing flavonoids are widely consumed, and their mechanisms of action are still only partially understood, this review was compiled to compare the effects and mechanisms of action of some of the most widely characterized and publicized flavonoids. The flavonoids silibinin, quercetin, isorhamnetin, luteolin, curcumin genkwanin, and acacetin, together with flavonoid extracts from papaw and Tephroseris kirilowii (Turcz) Holub, a member of the Daisy family, were found to be potent regulators of the cell cycle. The decision to overview these specific flavonoids was based on their therapeutic effects, and/or their potential effects. The sparsity of data comparing these flavonoids was also a key consideration. These flavonoids all modulated to some extent the pathways of autophagy and/or apoptosis and regulated the cell cycle, inflammation, and free radical levels. This explains why they are protective of healthy or moderately damaged cells, but toxic to neoplastic or pre-cancerous cells.

Keywords: apoptosis; autophagy; cancer; curcumin; flavonoids; phytochemicals.