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

Frontiers in Oncology

Jean C. Li¹  Wang Liu¹  Jeffrey Holzbeierlein¹  Benyi Li²  Jian Huang²  Jiepeng Chen³ 

[1] Department of Urology, The University of Kansas Medical Center, Kansas City, KS, United States;Institute of Molecular Pathology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang, China;Sungen Bioscience Institute, Shantou, China;

关键词: Alternol;    Alteronol;    apoptosis;    cell cycle;    radical oxygen species;    Cladosporol;   

DOI  :  10.3389/fonc.2020.568110

来源: DOAJ

【 摘 要 】

Alternol and its oxidate isomer Alteronol are small compounds isolated from the fermentation of a mutant fungus obtained from Taxus brevifolia 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.

【 授权许可】

Unknown