Danthron induces DNA damage and inhibits DNA repair gene expressions in GBM 8401 human brain glioblastoma multiforms cells.
Our primary studies had shown that danthron induced cytotoxic effects, including apoptosis and inhibition of migration and invasion. However, danthron-affected DNA damage and repair gene expressions are not clear. In this study, we investigated to examine whether or not danthron induced DNA damage and inhibited DNA repair gene expression in human brain glioblastoma multiforms (GBM 8401) cells. The results from Comet assay indicated that incubation of GBM 8401 cells with 0, 50, 100 and 150 microM of danthron led to a longer DNA migration smear based on the single cell electrophoresis (Comet tail). The results from real-time PCR assay demonstrated that 100 microM of danthron for 24 h treatment in GBM 8401 cells led to decrease all examined ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR), breast cancer 1, early onset (BRCA-1), 14-3-3 proteins sigma (14-3-3sigma), DNA-dependent serine/threonine protein kinase (DNA-PK) and O ( 6 )-methylguanine-DNA methyltransferase (MGMT) mRNA expressions. Taken together, the present study showed that danthron caused DNA damage and inhibited DNA repair genes, which may be the factors for danthron-inhibited cell growth in vitro.
Lu
Hsu-Feng
HF
Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei, Taiwan.
Lai
Tung-Yuan
TY
Hsia
Te-Chung
TC
Tang
Yih-Jing
YJ
Yang
Jai-Sing
JS
Chiang
Jo-Hua
JH
Lu
Chi-Cheng
CC
Liu
Chi-Ming
CM
Wang
Hai-Lung
HL
Chung
Jing-Gung
JG
D000880:Anthraquinones / Q000009:adverse effects*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans
D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic; C004315:danthron