Thymoquinone induces telomere shortening, DNA damage and apoptosis in human glioblastoma cells.
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.
Gurung
Resham Lal
RL
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Lim
Shi Ni
SN
Khaw
Aik Kia
AK
Soon
Jasmine Fen Fen
JF
Shenoy
Kirthan
K
Mohamed Ali
Safiyya
S
Jayapal
Manikandan
M
Sethu
Swaminathan
S
Baskar
Rajamanickam
R
Hande
M Prakash
MP
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
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