Caffeic acid phenethyl ester preferentially enhanced radiosensitizing and increased oxidative stress in medulloblastoma cell line
Caffeic acid phenethyl ester (CAPE), an active component of propolis, was recently reported to have radiosensitizing effects on medulloblastoma (MB) cells. However, the mechanisms of radiosensitivity involved in medulloblastoma cells are still unclear. The specific aim of this study was to investigate the role of CAPE-induced oxidative stress to influence of radiosensitivity and anti-proliferative effects in medulloblastoma cells.
Materials and methods
Medulloblastoma (Daoy) cells were treated with CAPE in different concentrations and assessed for cell viability. The following were also evaluated: migratory ability, reduced glutathione (GSH) level, reactive oxygen species (ROS) level, nuclear factor-kappaB (NF-κB) activity, and apoptosis in CAPE alone, radiation alone, or radiation combined with CAPE in Daoy cells.
The results indicated that CAPE inhibited the growth of Daoy cells. CAPE treatment in Daoy cells could effectively decrease glutathione reductase and significantly increase glutathione peroxidase. Radiation-activated NF-κB was reversed by CAPE pretreatment. Finally, the result of terminal deoxynucleotidyl transferase-mediated dUTP–biotin nick end labeling assay showed that CAPE treatment can enhance radiation-induced apoptosis in Daoy cells.
Our study demonstrated the anti-proliferative and radiosensitizing effects of CAPE on MB cells, which may be achievable through depleting GSH, increased ROS activity, and inhibiting NF-κB activity.
KeywordsCaffeic acid phenethyl ester (CAPE) Medulloblastoma Radiosensitivity Nuclear factor-kappaB (NF-κB) Glutathione (GSH) Reactive oxygen species (ROS)
This study was supported by research grants from the National Science Council (NSC-96-3111-B-075-001, 96-2628-B-010-006-MY3), Taipei Veterans General Hospital (V97E1-008, V97F-001), Yen-Tjing-Ling Medical Foundation, Taipei City Hospital (96001-62-014, 96001-62-018, 96002-62-092), and National Yang-Ming University (Ministry of Education, Aim for the Top University Plan), Taiwan.
- 8.Chiou SH, Kao CL, Lin HT, Tseng WS, Liu RS, Chung CF, Ku HH, Lin CP, Wong TT (2006) Monitoring the growth effect of xenotransplanted human medulloblastoma in an immunocompromised mouse model using in vitro and ex vivo green fluorescent protein imaging. Child’s Nerv Syst 22(5):475–480CrossRefGoogle Scholar
- 16.Hoppe-Hirsch E, Brunet L, Laroussinie F, Cinalli G, Pierre-Kahn A, Renier D, Sainte-Rose C, Hirsch JF (1995) Intellectual outcome in children with malignant tumors of the posterior fossa: influence of the field of irradiation and quality of surgery. Child’s Nerv Syst 11:340–346CrossRefGoogle Scholar
- 26.Michaluart P, Masferrer JL, Carothers AM, Subbaramaiah K, Zweifel BS, Koboldt C, Mestre JR, Grunberger D, Sacks PG, Tanabe T, Dannenberg AJ (1999) Inhibitory effects of caffeic acid phenethyl esteron on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in rat model of inflammatory. Cancer Res 59:2347–2352PubMedGoogle Scholar