Figure 1. Perifosine induces telomere shortening in vitro.

Initial testing indicated that Perifosine treatment induced telomere shortening over 20 population doublings of exposure in a variety of cancer cell types, while Perifosine did not accelerate telomere shortening in the telomerase negative BJ fibroblast line A., though there was a large degree of heterogeneity in response to Perifosine. Prolonged treatment with Perifosine (70 population doublings) led to further telomere shortening in Hela cells, while not accelerating shortening in BJ cells B., indicating that long-term treatment with Perifosine could result in continuous telomere shortening. Perifosine treatment had variable effects on telomerase enzymatic activity C., measured as number of telomerase extension products per cell input, though changes in enzymatic activity were not always consistent with changes in telomere length. Continuous long-term treatment with Perifosine interfered with colony formation and growth in soft agar D., suggesting that it may be a viable anti-telomerase therapy.