title: Lichen secondary metabolites are responsible for induction of apoptosis in HT-29 and A2780 human cancer cell lines.
abstract: Lichens are a known source of approximately 800 unique secondary metabolites, many of which play important ecological roles, including regulating the equilibrium between symbionts. However, only a few of these compounds have been assessed for their effectiveness against various in vitro cancer models. Moreover, the mechanisms of biological activity of lichen secondary metabolites on living cells (including cancer cells) are still almost entirely unknown. In the present study, we investigated the mechanisms of cytotoxicity of four lichen secondary metabolites (parietin, atranorin, usnic acid and gyrophoric acid) on A2780 and HT-29 cancer cell lines. We found that usnic acid and atranorin were more effective anti-cancer compounds when compared to parietin and gyrophoric acid. Usnic acid and atranorin were capable of inducing a massive loss in the mitochondrial membrane potential, along with caspase-3 activation (only in HT-29 cells) and phosphatidylserine externalization in both tested cell lines. Induction of both ROS and especially RNS may be responsible, at least in part, for the cytotoxic effects of the tested compounds. Based on the detection of protein expression (PARP, p53, Bcl-2/Bcl-xL, Bax, p38, pp38) we found that usnic acid and atranorin are activators of programmed cell death in A2780 and HT-29, probably through the mitochondrial pathway.
authors.affiliation: Institute of Biology and Ecology, Department of Cellular Biology, Pavol Jozef Šafárik University in Košice, Slovakia. peter.fedorocko@upjs.sk
authors.forename: M
authors.initials: M
authors.lastname: Bačkorová
authors.forename: R
authors.initials: R
authors.lastname: Jendželovský
authors.forename: M
authors.initials: M
authors.lastname: Kello
authors.forename: M
authors.initials: M
authors.lastname: Bačkor
authors.forename: J
authors.initials: J
authors.lastname: Mikeš
authors.forename: P
authors.initials: P
authors.lastname: Fedoročko
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D008011:Lichens / Q000737:chemistry / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D053148:Caspase 3