The Comprehensive Roles of ATRANORIN, A Secondary Metabolite from the Antarctic Lichen Stereocaulon caespitosum, in HCC Tumorigenesis

Abstract

Hepatocellular carcinoma (HCC) is one of the most deadly genetic diseases, but surprisingly chemotherapeutic approaches against HCC are only limited to a few targets. In particular, considering the difficulty of a chemotherapeutic drug development in terms of cost and time enforces searching surrogates to minimize effort and maximize efficiency in anti-cancer therapy. In spite of the report that around a thousand of lichen-derived metabolites have been isolated, the knowledge about its functions and consequences in cancer development are relatively little. Moreover, one of the major second metabolites from lichens, atranorin has been never studied in HCC. Regarding this, we comprehensively analyze the effect of atranorin by employing representative HCC cell lines and experimental approaches. Cell proliferation and cell cycle analysis using the compound consistently show the inhibitory effects of atranorin. Moreover, cell death determination using Annexin-V and PI staining suggests that it induces cell death through necrosis. Lastly, the metastatic potential of HCC cell lines is significantly inhibited by the drug. Taken these together, we claim a novel functional finding that atranorin comprehensively suppresses HCC tumorigenesis and metastatic potential, which could provide an important basis for anti-cancer therapeutics.