title: Thymoquinone induces telomere shortening, DNA damage and apoptosis in human glioblastoma cells.
abstract: BACKGROUND
  A major concern of cancer chemotherapy is the side effects caused by the non-specific targeting of both normal and cancerous cells by therapeutic drugs. Much emphasis has been placed on discovering new compounds that target tumour cells more efficiently and selectively with minimal toxic effects on normal cells.
  
  
  RESULTS
  The cytotoxic effect of thymoquinone, a component derived from the plant Nigella sativa, was tested on human glioblastoma and normal cells. Our findings demonstrated that glioblastoma cells were more sensitive to thymoquinone-induced antiproliferative effects. Thymoquinone induced DNA damage, cell cycle arrest and apoptosis in the glioblastoma cells. It was also observed that thymoquinone facilitated telomere attrition by inhibiting the activity of telomerase. In addition to these, we investigated the role of DNA-PKcs on thymoquinone mediated changes in telomere length. Telomeres in glioblastoma cells with DNA-PKcs were more sensitive to thymoquinone mediated effects as compared to those cells deficient in DNA-PKcs.
  
  
  CONCLUSIONS
  Our results indicate that thymoquinone induces DNA damage, telomere attrition by inhibiting telomerase and cell death in glioblastoma cells. Telomere shortening was found to be dependent on the status of DNA-PKcs. Collectively, these data suggest that thymoquinone could be useful as a potential chemotherapeutic agent in the management for brain tumours.
authors: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors: Resham Lal
authors: RL
authors: Gurung
authors: Shi Ni
authors: SN
authors: Lim
authors: Aik Kia
authors: AK
authors: Khaw
authors: Jasmine Fen Fen
authors: JF
authors: Soon
authors: Kirthan
authors: K
authors: Shenoy
authors: Safiyya
authors: S
authors: Mohamed Ali
authors: Manikandan
authors: M
authors: Jayapal
authors: Swaminathan
authors: S
authors: Sethu
authors: Rajamanickam
authors: R
authors: Baskar
authors: M Prakash
authors: MP
authors: Hande
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D009687:Nuclear Proteins; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D019098:Telomerase; C003466:thymoquinone