Differential Pharmacological Activities of Oxygen Numbers on the Sulfoxide Moiety of Wasabi Compound 6-(Methylsulfinyl) Hexyl Isothiocyanate in Human Oral Cancer Cells.

6-(methylsulfinyl) hexyl isothiocyanate (6-MITC) is a naturally occurring compound isolated from Wasabia japonica (wasabi). The synthetic derivatives, 6-(methylsulfenyl) hexyl isothiocyanate (I7447) and 6-(methylsulfonyl) hexyl isothiocyanate (I7557), were derived from 6-MITC with the deletion and addition of oxygen, respectively. We aimed to evaluate the effect of these synthetic compounds on human oral cancer cells, SAS and OECM-1. All three compounds (I7447, 6-MITC, and I7557) inhibited the viability of SAS and OECM-1 cells using MTT assay. Morphological observations showed various proportions of mitotic arrest and apoptosis in cells treated with these compounds. Cell cycle analysis revealed relatively abundant G2/M arrest in 6-MITC and I7557-treated cells, whereas sub-G1 accumulation was found in I7447-treated cells. In using phosphorylated histone H3 as a marker for mitosis, the addition of 6-MITC and I7557 (excluding I7447) could be shown to arrest cells during mitosis. In contrast, I7447 induced more prominent apoptosis than the 6-MITC or I7557 compounds. The down-regulated expression of the phosphorylated form of CHK1 and Cdc25c was noted in 6-MITC and I7557-treated cells. I7557 could sensitize SAS cells to death by radiation. The wasabi compound, 6-MITC, and its chemical derivatives with different numbers of oxygen may have differential pharmacological effects on human oral cancer cells.

Antiproliferation and radiosensitization of caffeic acid phenethyl ester on human medulloblastoma cells.

PURPOSE: To investigate antiproliferative and radiosensitizing effects of caffeic acid phenethyl ester (CAPE) on medulloblastoma (MB) Daoy cells. METHODS AND MATERIALS: Daoy cells were treated with CAPE in different concentrations and assessed for cell viability, apoptosis, cell cycles, cyclin B1 expressions, radiosensitization and chemosensitization. Human astroglia SVGp12 cells were treated with CAPE to present the possible protection or complication effects in normal tissues. RESULTS: CAPE inhibited the growth of Daoy cells in a time- and concentration-dependent manner in MTT and Trypan blue exclusion assays. Flow cytometry revealed that CAPE significantly decreased G2/M fraction, and increased the S phase fraction. Western blot demonstrated a down-regulated cyclin B1 protein expression. Pretreatment with CAPE markedly decreased the viability of irradiated Daoy cells. The sensitizer enhancement ratios (SERs) were increased in CAPE-treated Daoy cells. CAPE in doxorubicin and cisplatin did not show chemosensitizing effect. CONCLUSIONS: These findings demonstrate the antiproliferative and radiosensitizing effects of CAPE for Daoy cells, which might bring improvement to the treatment of MB. For clinical application, in vivo models are expected.

Monitoring the growth effect of xenotransplanted human medulloblastoma in an immunocompromised mouse model using in vitro and ex vivo green fluorescent protein imaging.

INTRODUCTION: Medulloblastoma (MB) is one of the most common malignant brain tumors in children. It is a radiosensitive tumor. At 5 years after radical surgical excision and craniospinal axis irradiation, the tumor-free survival rate is from 50 to 70% [Halperin EC, Constine LS, Tarbell NJ, Kun LE. Pediatric radiation oncology (2005)]. CASE REPORT: In this study, we established xenotransplanted human MB (hMB) cells - isochromosome 17q - in a severe combined immunodeficiency (SCID) mouse model. We further transduced green fluorescent protein (GFP) into hMB cells to evaluate these hMB cells grafted in SCID mice. RESULTS: The result of an ex vivo GFP imaging system showed that a small lesion of the third-week-hMB-transplanted graft presented "green" signals with a clear tumor margin before any tumor-related symptoms were noted. We also demonstrated that the tumor progression could be monitored by GFP imaging for up to 12 weeks post-transplantation. CONCLUSIONS: This novel approach of GFP imaging assessment provides more accurate information of tumor status for experimental brain tumor studies. Because MB is sensitive to radiation and also response to chemotherapy, this SCID mouse model will be helpful for preclinical studies in the future.

Apoptosis of human retina and retinal pigment cells induced by human cytomegalovirus infection.

Human cytomegalovirus (HCMV) retinitis is the most common ocular opportunistic infection in immunocompromised patients and AIDS. It often leads to blindness if left untreated. The question as to how HCMV infection causes retinal pathogenesis and visual destruction in AIDS patients remains unresolved. To answer the question, by using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay, we detected the significant signals of apoptotic cells at the same sites in the HCMV-infected retina of AIDS patients as compared to AIDS patients without HCMV retinitis. In vitro study also revealed apoptosis induced by HCMV infection in human retinal pigment epithelium cells, mediated by activation of caspase 3 and poly(ADP-ribose) polymerase pathway. These results strongly suggest the fundamental role of HCMV-induced apoptosis in mediating cell death in infected human retina and retinal pigment epithelium cells to make severe visual impairment.