Anticancer Polyphenols from Cultured Plant Cells: Production and New Bioengineering Strategies.

BACKGROUND: For many years, anticancer polyphenols have attracted significant attention as substances that prevent tumor growth and progression. These compounds are simple phenolic acids, complex phenolic acids, such as caffeoylquinic acids, rosmarinic acid and its derivatives, stilbenes, flavones, isoflavones, and anthocyanins. Some compounds, such as tea and coffee polyphenols, can be produced in large quantities by traditional methods, while many others cannot. METHODS: We reviewed the available literature regarding the biotechnological aspects of polyphenol production by cultured plant cells and described approaches that have been used to obtain high levels of anticancer polyphenols (resveratrol, podophyllotoxin, genistein, lithospermic acid B, and others). Additionally, we provide our view on bioengineering strategies that could be important for the further improvement of cell biosynthetic characteristics. RESULTS: The main trend in the field is the activation of entire biosynthetic pathways based on a comprehensive knowledge of protein-protein interaction networks involved in the regulation of polyphenol biosynthesis. As an example, we consider the jasmonate subnetwork, which will be increasingly used by plant biotechnologists. The next-generation technologies to sustained polyphenol production involve manipulations with microRNAs and reproduction of rol-gene effects. CONCLUSION: Plant polyphenols play an important role in maintaining human health, and their role in the prevention of cancer will continue to grow. Targeting mechanisms involved in uncontrolled cancer cell proliferation will increasingly become the standard for cancer patients. Plant biotechnological studies aiming at producing anticancer compounds will be developed in parallel with these studies to provide a wider range of metabolites for each particular case.

The rolC gene increases caffeoylquinic acid production in transformed artichoke cells.

Caffeoylquinic acids are found in artichokes, and they are currently considered important therapeutic or preventive agents for treating Alzheimer's disease and diabetes. We transformed artichoke [the cultivated cardoon or Cynara cardunculus var. altilis DC (Asteraceae)] with the rolC gene, which is a known inducer of secondary metabolism. High-performance liquid chromatography with UV and high-resolution mass spectrometry (HPLC-UV-HRMS) revealed that the predominant metabolites synthesized in the transgenic calli were 1,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, and chlorogenic acid. The rolC-transformed calli contained 1.5% caffeoylquinic acids by dry weight. The overall production of these metabolites was three times higher than that of the corresponding control calli. The enhancing effect of rolC remained stable over long-term cultivation.