Abstract 1598: Isothiocyanates promote cell death and sensitize glioblastoma cells to radiation.

Abstract Sulforaphane (SFN) and beta-phenylethyl isothiocyanate (PEITC), are organic isothiocyanate compounds found in dietary cruciferous vegetables with previously characterized anti-proliferative properties; and more recently, pro-apoptosis capabilities in several tumor types. The present study was designed to determine the role of isothiocyanates, particularly SFN and PEITC in vitro with human glioblastomas cells; and in vivo with a murine orthotropic glioblastoma tumor model. Cultured glioblastoma cells were treated with SFN in increasing doses to 80 μM and PEITC to 20 μM. Cells were examined for changes in morphology characteristic of apoptosis and with MTT for cell survival. Cells were exposed to both isothiocyanates either alone or in combination. Our results indicate that SFN inhibits cell proliferation as well as the activation of apoptosis in three GBM cell lines, LD50 for SFN was at 25 μM and essentially kill all the cells at 50 μM 24 hours post-treatment. In three cell lines the LD50 of PEITC is 5 μM and loss of all the cells at 10μM. Treatment with SFN 10 μM and PEITC 5 μM promoted cell death to 80% in which cause 10% and 30% die in U87 cells respectively. Furthermore, exposure of DBT cells to SFN at 10 μM as well as radiation at 2.5Gy, 5Gy and 7.5 Gy resulted in remarkably decreased of clones formation comparing to radiation only. Yield rate of control only, SFN only, 2.5Gy only and SFN+2.5GY are 70.5, 12.7%, 4.8% and 0.62% respectively. While visible clones were existed at 7.5 Gy only, it was barely existing at 7.5Gy with SFN. In vivo studies with subcutaneous murine DBT glioblastoma tumors which treated with SFN daily IP injection for 5 days at dose 12.5mg/kg, decreased tumor size based on weight by 28% compared with those treated with vehicle only. PEITC at 25mg/kg only had failed to decrease the tumor on weight. However, SFN combine with PEITC decreased the GBM on weight by 68% (P =0.016, less than 0.05). This decrease in tumor weight was significantly different as assessed with a two-tailed Students’ t-test for independent variables. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was assessed for apoptosis. The results are: vehicle-only (0.4+0.06%)(n=8); vehicle-only+SFN (1.9+0.3%)(n=8); PEITC (0.9+1.2%)(n=8); and SFN+PEITC (3.6+0.1%)(n=9), demonstrated a significantly greater incidence of apoptosis compared with the vehicle-only group as determined with a two-tailed Students’ t-test for independent variables. These studies supported SFN as a potential anti-tumor drug to promote cell death and enhance of radiosensitivity in glioblastomas in vivo. Our findings suggest that, in addition to the known effects on cancer prevention, isothiocyanates should be viewed as a therapeutic advantage in established malignant glioma. Citation Format: Liya Yuan, Xuan Ren, Jerry Jaboin, Jonathan McConathy, Keith M. Rich. Isothiocyanates promote cell death and sensitize glioblastoma cells to radiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1598. doi:10.1158/1538-7445.AM2013-1598