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

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.

Cancer cells that survive checkpoint adaptation contain micronuclei that harbor damaged DNA

“…In addition, these cells have several complex chromosomal rearrangements, including reciprocal and non-reciprocal translocations. 24 Although the precise mechanism is not known, it is possible that the absence of functional p53 enables cells to tolerate genomic change better than cells with p53. 25 Variability in chromosome number and genomic rearrangements are frequently associated with the presence of micronuclei.…”

Plumbagin alters telomere dynamics, induces DNA damage and cell death in human brain tumour cells

“…Due to the differential expression of telomerase in cancer cells and normal somatic cells, targeting the telomere dynamics has been considered an attractive option in chemotherapy today [17][18][19]. In this regard, we have recently shown that certain natural plant products possess the ability to inhibit telomerase and subsequently induce cell death in human cancer cells [20][21][22]. To the best of our knowledge, there is no report on the effect of plumbagin on telomere dynamics in cancer cells.…”

Protective effect of thymoquinone against cyclophosphamide-induced genotoxic damage in human lymphocytes

“…In vitro studies show that TQ can inhibit growth of several types of cancer cells. Such anti-proliferative activities exhibited by TQ involve inhibition of cancer cell signal transduction and apoptosis, which consequently leads to reduced DNA oxidative damage (4,7,8). It also controls the Akt pathway, which means it controls the process that manages cell survival for both normal and cancer cells (18).…”

“…TQ has been demonstrated as a cytotoxic agent in several multi-drug resistant human tumor cell lines. Molecular mechanisms underlying these anticancer effects were attributed to inductions of cell cycle arrest, apoptosis, oxidative damage of cellular macromolecules, blockade of tumor angiogenesis and inhibitions in migration, invasion and metastasis of cancer cells and TQ induces DNA damage, telomere attrition by inhibiting telomerase and cell death in cancer cells (6,7). Also, the combination of TQ and conventional chemotherapeutic agents could produce greater therapeutic effect as well as enhance cytotoxic effect in tumor cells (8).…”