Cancers, Vol. 14, Pages 3122: Cordycepin (3 & prime;-Deoxyadenosine) Suppresses Heat Shock Protein 90 Function and Targets Tumor Growth in an Adenosine Deaminase-Dependent Manner

Cancers, Vol. 14, Pages 3122: Cordycepin (3′-Deoxyadenosine) Suppresses Heat Shock Protein 90 Function and Targets Tumor Growth in an Adenosine Deaminase-Dependent Manner Cancers doi: 10.3390/cancers14133122 Authors: Su-Chan Lee Lujain Alaali HyukJean Kwon Mohammed Rigi Charles G. Eberhart Alterations in metabolism and energy production are increasingly being recognized as important drivers of neoplasia, raising the possibility that metabolic analogs could disrupt oncogenic pathways. 3′-deoxyadenosine, also known as cordycepin, is an adenosine analog that inhibits the growth of several types of cancer. However, the effects of cordycepin have only been examined in a limited number of tumor types, and its mechanism of action is poorly understood. We found that cordycepin slows the growth and promotes apoptosis in uveal melanoma, as well as a range of other hard-to-treat malignancies, including retinoblastoma, atypical teratoid rhabdoid tumors, and diffuse midline gliomas. Interestingly, these effects were dependent on low adenosine deaminase (ADA) expression or activity. Inhibition of ADA using either siRNA or pharmacologic approaches sensitized tumors with higher ADA to cordycepin in vitro and in vivo, with increased apoptosis, reduced clonogenic capacity, and slower migration of neoplastic cells. Our studies suggest that ADA is both a biomarker predicting response to cordycepin and a target for combination therapy. We also describe a no...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research