Discovery of Survivin Inhibitors Part 1: Screening the Harbor Branch Pure Compound Library

Marine Drugs

EstherA. Guzmán¹  TaraP. Pitts¹  PriscillaL. Winder¹  AmyE. Wright¹  KirstieR. Tandberg¹ 

[1] Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1, Fort Pierce, FL 34946, USA;

关键词: survivin;    eryloside E;    ilicicolin H;    tanzawaic acid A;    high content imaging;   

DOI  :  10.3390/md19020073

来源: DOAJ

【 摘 要 】

Survivin is a 16.5 KDa protein whose functions include promoting cellular mitosis, angiogenesis, and senescence as well as inhibiting apoptosis. Higher survivin expression is found in cancer tissues than normal tissues, and this expression correlates with disease progression and aggressiveness. Survivin has been validated as a clinical target for cancer. Small molecules are important antagonists of survivin levels in cancer cells. A structurally diverse library of genetically encoded small molecules (natural products) derived from marine plants, invertebrates, and microbes was screened for their ability to reduce expression levels of survivin in the DLD-1 colon adenocarcinoma and the A549 nonsmall cell lung carcinoma cell lines. This led to the identification of this novel activity for the known compounds eryloside E, ilicicolin H, tanzawaic acid A, and p-hydroxyphenopyrrozin. Both eryloside E and ilicicolin H showed the ability to reduce survivin expression in the low micromolar range against both cell lines.

【 授权许可】

Unknown