Polyphenols as mitochondria-targeted anticancer drugs.

Mitochondria are the respiratory and energetic centers of the cell where multiple intra- and extracellular signal transduction pathways converge leading to dysfunction of those organelles and, consequently, apoptotic or/and necrotic cell death. Mitochondria-targeted anticancer drugs are referred to as mitocans; they have recently been classified by Neuzil et al. (2013) according to their molecular mode of action into: hexokinase inhibitors; mimickers of the Bcl-2 homology-3 (BH3) domains; thiol redox inhibitors; deregulators of voltage-dependent anionic channel (VDAC)/adenine nucleotide translocase (ANT) complex; electron redox chain-targeting agents; lipophilic cations targeting the mitochondrial inner membrane; tricarboxylic acid cycle-targeting agents; and mitochondrial DNA-targeting agents.

Synergistic interactions between anticancer chemotherapeutics and phenolic compounds and anticancer synergy between polyphenols.

Chemoprevention has recently gained a new dimension due to the possibility of studying the mechanisms of action of chemopreventive agents at the molecular level. Many compounds have been proved to inhibit early stages of carcinogenesis in experimental models. These compounds include both recognized drugs (such as tamoxifen and nonsteroidal anti-inflammatory drugs) and natural constituents of edible and therapeutic plants, particularly polyphenols.

Overview of metabolism and bioavailability enhancement of polyphenols.

A proper diet is one of major factors contributing to good health and is directly related to general condition of the organism. Phenolic compounds are abundant in foods and beverages (fresh and processed fruits and vegetables, leguminous plants, cereals, herbs, spices, tea, coffee, wine, beer) and their pleiotropic biological activities result in numerous health beneficial effects. On the other hand, high reactivity and very large diversity in terms of structure and molecular weight renders polyphenols one of the most difficult groups of compounds to investigate, as evidenced by ambiguous and sometimes contradictory results of many studies.

Procyanidins from Japanese quince (Chaenomeles japonica) fruit induce apoptosis in human colon cancer Caco-2 cells in a degree of polymerization-dependent manner.

Plant proanthocyanidins, including procyanidins, display various biological activities. Here we report an inhibition of human colon cancer Caco-2 cell growth by the extract from Japanese quince fruit and the procyanidin-rich fractions of the extract. We observed that the amount of apoptotic Caco-2 cells increased by 52.

Polyphenols from evening primrose ( Oenothera paradoxa ) defatted seeds induce apoptosis in human colon cancer Caco-2 cells.

Polyphenols extracted from evening primrose seeds (industrial waste product) were studied as apoptosis inducers in human colorectal adenocarcinoma Caco-2 and HT-29 cell lines and in rat normal intestinal IEC-6 cells. The extract dose-dependently inhibited the growth of Caco-2, HT-29, and IEC-6 cells. However, nuclear DNA fragmentation characteristic of apoptosis was observed only in Caco-2.

Procyanidin oligomers from Japanese quince (Chaenomeles japonica) fruit inhibit activity of MMP-2 and MMP-9 metalloproteinases.

The influence of procyanidin extract from Japanese quince fruit on the activities of matrix metalloproteinases MMP-2 and MMP-9 secreted to culture medium by human peripheral blood mononuclear cells (PBMC) and by human leukemia HL-60 cells was investigated by gelatin zymography. The extract proved to be an effective inhibitor of the enzymes activities (for MMP-2 and MMP-9 secreted by PBMC IC50 = 16-19 microg extract/mL and 22-25 microg extract/mL, respectively). To identify the most effective components of the extract it was fractionated by means of column chromatography on TSKgel Toyopearl HW-40 (S) bed.