Thymoquinone Induces Telomere Shortening, DNA Damage and Apoptosis in Human Glioblastoma Cells

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

doi:10.1371/journal.pone.0012124

Abstract

BackgroundA 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 FindingsThe 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/SignificanceOur 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.

Highlights

A major concern of cancer chemotherapy is the side effects induced by the non-specific targeting of both normal and cancerous cells by chemotherapeutic drugs
Our findings demonstrate that at selective dose of TQ, glioblastoma cells were more sensitive to TQ-induced damage as compared to normal cells as indicated by the higher levels of apoptosis and reduced cell viability
Thymoquinone reduced the viability of the human brain cancer cells more effectively than non-cancerous cells

Summary

Introduction

A major concern of cancer chemotherapy is the side effects induced by the non-specific targeting of both normal and cancerous cells by chemotherapeutic drugs. Much emphasis has been placed on discovering new compounds that target cancer cells with minimal toxicity to normal cells. Various natural compounds have been shown to be promising chemotherapeutic agents with lesser cytotoxicity to the normal cells [1]. TQ has been demonstrated as a cytotoxic agent in several multi-drug resistant human tumour cell lines [6]. 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

Methods

Results

Conclusion