Investigation of the angiogenesis-targeted treatment potentials of the small molecule structured natural compounds by epigenetic approach and molecular mechanisms on tumor development and invasion

Lichens are symbiotic associations, formed as a result of a participation of fungus and algae, and more than 1000 unique compounds can be synthesized due to the advanced metabolic relationship within this association. Although there are a lot of studies about anti-inflammatory, anti-pyretic, analgesic, ultraviolet protective, enzyme inhibitor, cytotoxic etc. activities of the lichen compounds, there are a few studies about their activities on angiogenesis. However, angiogenesis is defined as the formation of new capillaries from existing blood vessels, considered as an important target in cancer treatment and the growth, development, tissue formation and metastasis of tumor cells. Therefore; cytotoxic activities of the lichen compounds named alectoronic acid, collatolic acid and caperatic acid on healthy and cancer cell lines; were determined by using MTT and Alamar Blue cell viability, LDH cellular membrane integrity and PicoGreen dsDNA quantitation assays, and their time-dependent toxicities were lighted up by using xCELLigence Real Time Cell Analysis MP (RTCA-MP) instrument. Their activities on angiogenesis and endothelial cell migration were determined by using endothelial tube formation assay and RTCA DP instrument, respectively. Furthermore, the activities on reactive oxygen species accumulation, oxidative DNA damage, cell adhesion, tumor cell invasion and DNA methylation were also investigated. Caperatic acid takes over as a most effective compound due to its low cytotoxicity and high anti-angiogenic activity. However, it has been determined, as a result of the accomplished experiments by using healthy and cancerous cells, that the all isolated compounds are promising for cancer treatment.