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Article Publish Status: FREE
Abstract Title:

Thymoquinone induces telomere shortening, DNA damage and apoptosis in human glioblastoma cells.

Abstract Source:

PLoS One. 2010 Aug 12 ;5(8):e12124. Epub 2010 Aug 12. PMID: 20711342

Abstract Author(s):

Resham Lal Gurung, Shi Ni Lim, Aik Kia Khaw, Jasmine Fen Fen Soon, Kirthan Shenoy, Safiyya Mohamed Ali, Manikandan Jayapal, Swaminathan Sethu, Rajamanickam Baskar, M Prakash Hande

Article Affiliation:

Resham Lal Gurung

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.

METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.

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