S-PAC-1, a small molecule activator of procaspase 3, sensitizes human breast cancer and other cell lines to ionizing radiation.

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NCI	CLIN/TRANS-1

* FARE Award Winner

Authors

• Gopal Abbineni
• Kheem Bisht
• Howar Roth
• Paul Hergenrothe
• Karl Haglund

Abstract

S-PAC-1, a small molecule activator of procaspase 3, exhibits potent anti-tumor activity in animal models with a favorable toxicity profile. Therefore, we investigated S-PAC-1 as a potential radiation sensitizer in human cancer cell lines .The in vitro radiosensitizing effects of S-PAC-1 on human cancer cell lines (MDA MB231, SF295, DU145, and Mia PaCa2 cells) were tested using clonogenic assays. DNA double strand breaks were evaluated using fluorescent microscopy. Cell cycle analysis and apoptosis were examined using flow cytometry. Incubation of cultured cells with concentrations of S-PAC-1 between 2.5 and 25 μM for 24 h followed by exposure to IR showed a DEF of 1.28 & 1.48 respectively. No significant radiation induced apoptosis was noticed. As a measure of DNA double strand breaks, γH2AX foci were quantitated at specified time points after drug S-PAC-1 pre-treatment and IR treatment. Increased foci formation was observed after S-PAC-1 pre-treatment. In addition, the presence of drug correlated with delayed dispersal of radiation induced γH2AX foci. In conclusion, S-PAC-1 has effectively enhanced the radiosensitivity of human cancer cell lines in vitro with DEFs of approximately 1.3. Because DSB induction and repair are key determinants of radiosensitivity, our results suggest that S-PAC-1 is a novel radiation sensitizer.

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