Phenethyl Inhibits in Vivo Growth of Xenograft Tumors of Human Glioblastoma Cells Yu-Cheng Chou, Jing-Gung Chung, Meng-Ya Chang, Tomor Harnod, Hsu-Tung Lee, Chiung-Chyi Shen, Yea-Jiuan Liang Department of Neurosurgery, Neurological Institute, Taichung Veterans General Hospital; Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei; Departments of Biological Science and Technology, China Medical University, Taichung; Institute of Medical Sciences, Tzu Chi University, Hualien; Department of Neurosurgery, Hualien Tzu Chi General Hospital, Taiwan, R.O.C.

Introduction in GBM 8401 cells (Fig. 2B). These Conclusions Fig. 1C Phenethyl isothiocyanate (PEITC), a effects were in a dose-dependent The biological properties of PEITC can component in , manner. inhibit the growth of glioblastoma in can suppress the cell growth in vivo. These effects provide support for various human cancers. Our previous further investigations to determine the Fig. 1A studies showed that PEITC inhibited in potential use of PEITC as an anticancer vitro growth of human glioblastoma drug for glioblastoma. GBM 8401 cells through inducing apoptosis, inhibiting migration and Discussion invasion, altering the gene The in vivo effects of PEITC on different expressions. There are no reports cancer cell models including showing that PEITC inhibits glioblastoma, melanoma, lung and The effects on the body weights in glioblastoma tumor growth in vivo. colon cancers were reported (Ni et al., xenograft GBM 8401/luc2 cells-bearing 2014; Fuentes et al., 2015; Cheung et mouse models Methods al., 2010). PEITC can reduce the The tumor weights after they were GBM 8401 cells were inoculated Fig 2 ectopic xenograft tumor growth of GBM sacrificed on day 21 were significantly subcutaneously into the right hind leg 8401 cells in tumor weights and decreased by PEITC at both doses of each nude mouse. Mice with one volumes, through the induction of compared to the control group. a2: p < palpable tumor were randomly divided apoptosis by the increase of pro- 0.01 compared to that of the control; b1: p into 3 groups: the control, PEITC-10 apoptotic proteins, caspase-3 and Bax, < 0.05 compared to that of PEITC-10 and PEITC-20 groups treated with and the decrease of anti-apoptotic group. 0.1% dimethyl sulfoxide (DMSO), proteins, MCL-1, XIAP. PEITC 10 and 20 µmole/100 µl PBS Fig. 1B daily by oral gavage, respectively. The The effects of PEITC on the expressions of References volumes of palpable tumors were apoptosis associated proteins in GBM 1. Ni WY, Lu HF, Hsu SC, Hsiao YP, Liu KC, Liu estimated with bioluminescence JY, Ji BC, Hsueh SC, Hung FM, Shang HS, Chung 8401/luc2 cells-bearing mice. All samples imaging (BLI). All mice were sacrificed JG. 2014. Phenethyl isothiocyanate inhibits in were analyzed under microscopy at×100 vivo growth of subcutaneous xenograft tumors of 3 weeks after oral treatment. Tumor magnification and photographed. (A) human malignant melanoma A375.S2 cells. In and total body weights were Caspase-3 and Bax; (B) MCL-1 and XIAP. Vivo 28(5):891-4. measured. Caspase-3, and apoptosis 2. Fuentes F, Paredes-Gonzalez X, Kong AN. associated proteins were assessed by 2015. Dietary , Phenethyl Isothiocyanate, -3-Carbinol/3,3' immunohistochemistry. -Diindolylmethane: Anti-Oxidative Stress/Inflammation, Nrf2, Results The tumor growth, monitored by BLI was Epigenetics/Epigenomics and In Vivo Cancer Chemopreventive Efficacy. Curr Pharmacol Rep PEITC reduced tumor weight (Fig. 1A) significantly suppressed by PEITC 1(3):179-196. and volume (Fig. 1B) of GBM 8401 compared to the control group. a1: p < 3. Cheung KL, Khor TO, Huang MT, Kong AN. cells in mice significantly, whereas the 0.05, a2: p < 0.01 compared to that of the 2010. Differential in vivo mechanism of total body weight was not affected control; b1: p < 0.05, b2: p < 0.01 chemoprevention of tumor formation in azoxymethane/dextran sodium sulfate mice by (Fig. 1C). PEITC increased the levels compared to that of PEITC-10 group. PEITC and DBM. Carcinogenesis 31(5):880-5. of caspase-3 and Bax (Fig. 2A). and decreased the levels of anti-apoptotic proteins, MCL-1 (myeloid cell leukemia 1), and XIAP (X-linked inhibitor of apoptosis protein)