New data generated by Annamaria Biroccio and colleagues at the Regina Elena National Cancer Institute, Rome, have provided a molecular characterization of the anticancer effects of the molecule RHPS4.
RHPS4 was shown to trigger a rapid and potent ATR-mediated DNA damage response at telomeres in vitro in human transformed fibroblasts and melanoma cells.
When administered to mice transplanted with human tumor cells, RHPS4 induced telomere damage to the human tumor cells that resulted in tumor cell death by a process known as apoptosis. However, if the human tumor cells had been engineered to overexpress the telomere-protective factors TRF2 and POT1 RHPS4 had no anticancer effect.
The authors therefore suggest that targeting telomeres, TRF2, or POT1 might provide new approaches to treating individuals with cancer.
TITLE: Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect
AUTHOR CONTACT:
Annamaria Biroccio
Regina Elena National Cancer Institute, Rome, Italy.
Phone: 39-0652662569; Fax: 39-0652662592