Colletofragarone A2 Inhibits Cancer Cell Growth In Vivo and Leads to the Degradation and Aggregation of Mutant p53

• DOI: 10.1021/acs.chemrestox.2c00202
• Publication Date: 2022-08-26T21:49:30Z
• Authors: Yusaku Sadahiro; Yuki Hitora; Ichiro Kimura; Natsuko Hitora-Im...; Risako Onodera; Keiichi Motoyama; Sachiko Tsukamoto
• Keywords: Wild type

Mutant p53 not only loses its original tumor suppressor function but also acquires new abilities regarding oncogenic progression. Therefore, the strategy of targeting mutant has attracted attention for cancer therapy. We isolated colletofragarone A2 (CF) from fungus Colletotrichum sp. (13S020), which decreases levels in cells, and herein examine effect on p53. CF showed more potent cytotoxic activities cells with p53R175H structural mutants than those different statuses such as a DNA-contact mutant, wild-type, null cells. markedly decreased cell growth vivo using mouse xenograft model HuCCT1 (p53R175H) Cotreatment SK-BR-3 cycloheximide by promoting degradation. In presence MG-132, induced accumulation aggregated These results suggest that inhibits molecular chaperones HSP90.