Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect
J. Clin. Invest. Erica Salvati, et al. 117:3236 doi:10.1172/JCI32461 [Go to this article.]

Figure 6
RHPS4 is active as single agent in xenograft tumors by inducing telomere injury and apoptosis. (A) Mice were injected i.m with M14 melanoma, PC3 prostate, H460 non–small cell lung, CG5 breast, and HT29 colon carcinoma cells and, starting from day 6 after cell injection, when a tumor mass of about 300 mg was observed, treated i.v. with RHPS4 at 15 mg/kg for fifteen consecutive days (days 6–21). Mean tumor weights in untreated (filled squares) and RHPS4-treated (open squares) mice. Points represent mean (bars, SD). Arrow indicates the start of treatment. (B) Terminal restriction fragment measured by Southern blotting in the indicated tumors untreated (–) and treated with RHPS4 (+). (C–F) In situ apoptosis and proliferation measured by TUNEL (C and D) and Ki-67 (E and F) staining, respectively, in untreated (C and E) and RHPS4-treated M14 tumors (D and F). Original magnification, ×40. (G–J) Immunohistochemical analysis of γ-H2AX (G and H) and H&E (I and J) staining in untreated (G and I) and RHPS4-treated M14 tumors (H and J). Original magnification, ×40. Enlarged views (original magnification, ×80) showing γ-H2AX reactivity and atypical mitoses are reported on the right. Analyses performed on tumor tissues were carried out at the end of treatment (day 22 after tumor cell injection) and were repeated 3 times using 3 different tumors for each point. Representative images of 3 independent experiments with comparable results are shown.