Wang T, Kruse K, Osborne C, Schlauch K, Briggs LA, Brown LK, Andrews WH, Tersteege L, Tanglao S, Hickman D, Mohammadpour H, Foster CA.

The majority of cancer cell lines and human embryonic stem cells express the catalytic subunit of telomerase reverse transcriptase (hTERT), which maintains chromosomal ends through the addition of telomeric repeats. In normal somatic cells, telomerase transcription is repressed and the erosion of telomeres limits replicative lifespan and leads to cellular senescence. Transient pharmacologic activation of hTERT has the potential to delay senescence and extend human lifespan. TA-65, a natural compound derived from the Chinese herb Astragalus and licensed to T.A. Sciences by Geron Corporation, is purported to activate telomerase. C0057684, a compound identified by Sierra Sciences, LLC in a high throughput transient reporter assay, has been shown to induce transcription and translation of active hTERT in human lung fibroblasts as determined by RT-PCR and the telomeric repeat amplification protocol (TRAP), respectively. Here, we use DNA microarrays to examine the gene expression profile of MRC5 cells exposed to TA-65 and C0057684 to further characterize the activity of these compounds. Our results indicate that TA-65 has limited effects on global gene expression relative to control DMSO samples while C0057684 significantly alters expression patterns.