AUTHOR=Liu Wang , Li Jean C. , Huang Jian , Chen Jiepeng , Holzbeierlein Jeffrey , Li Benyi 

TITLE=Alternol/Alteronol: Potent Anti-cancer Compounds With Multiple Mechanistic Actions

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.568110

DOI=10.3389/fonc.2020.568110

ISSN=2234-943X

ABSTRACT=<p>Alternol and its oxidate isomer Alteronol are small compounds isolated from the fermentation of a mutant fungus obtained from <italic>Taxus brevifolia</italic> bark. Preclinical studies showed their potent anti-cancer activities, including attenuating cellular survival pathways, altering protein levels of cell cycle regulators, activating xanthine dehydrogenase to cause accumulation of cellular reactive oxygen species and disrupting cell metabolism by disturbing four Krebs cycle enzymes specifically in malignant cells while having no significant effect on benign cells. In cancer cell culture models, Alternol or Alteronol exert their anti-cancer effect by inducing cell cycle arrest and triggering apoptotic cell death. In mice xenograft models, Alternol or Alteronol potently suppresses tumor growth with no obvious toxicity to the host with a wide therapeutic index over 30-fold. In conclusion, Alternol or Alteronol possess a great potential and feasibility to be developed as an effective anti-tumor therapeutic.</p>