Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


I Racoma Dissertation.pdf (2.41 MB)

ETD Abstract Container

Abstract Header

Targeting Glioblastoma Survival Signaling: A Novel Mechanism of Action of Thymoquinone

Racoma, Ira Oliva
http://rave.ohiolink.edu/etdc/view?acc_num=osu1369923513

Abstract Details

2013, Doctor of Philosophy, Ohio State University, Integrated Biomedical Science Graduate Program.
Abstract Glioblastoma is a grade IV glioma and remains the most aggressive and devastating cancer of the central nervous system with a median survival of 15 months. It is the most common malignant brain tumor diagnosed in adults and accounts for 23% of all primary brain tumors. Adding to this statistic is the number of recurring tumors, which occurs in a vast majority of cases. Glioblastomas are resistant to treatment due to the upregulation of survival pathways, decreased expression in pro-apoptotic proteins and overexpression of anti-apoptotic proteins. There has been a growing interest in natural compounds with anti-cancer properties because they are relatively non-toxic to healthy cells and are available in a readily ingested form. The dietary phytochemical thymoquinone (TQ) is the primary bioactive component of Nigella sativa Linn seed (also known as black seed) oil which has been used for centuries in Middle Eastern, Indian and European countries for culinary purposes and to promote good health. We have previously shown that TQ induces apoptosis in HL-60 leukemia cells and MCF-7/DOX doxorubicin-resistant breast cancer cells. The work presented in this thesis describes the mechanism of action TQ in apoptosis-resistant glioblastoma cells. On the molecular level, TQ induced intense DSBs and cell cycle alterations. We found that TQ mediated these effects on DNA and the cell cycle via arylation of target molecules, and not via generation of reactive oxygen species. Additionally, TQ did not exert the same detrimental effects on normal human astrocytes, confirming reports of the selectivity of TQ for cancer cells. Glioblastoma are characterized by their resistance to apoptosis due to upregulation of several survival signaling pathways. In recent years, autophagy has emerged as a bona fide survival pathway for a number of tumors. TQ inhibited autophagy in glioblastoma cells, which was found to be a consequence of permeabilization of the lysosomal membrane. Additionally TQ induced the release of cathepsins into the cytosol which can mediate caspase-independent death in apoptosis-resistant cells. Finally, TQ was tested in vivo by evaluating the survival time of mice with intra-cranial tumors. TQ resulted in a promising increase of survival time in treated mice. Orally administered drug did not result in adverse reactions and appears to be able to reach a neurological tumor site. The significance of this work was to investigate the modulation of a novel tumor survival pathway with a natural compound in the hopes of shedding light on new approaches to the treatment of a recalcitrant tumor.
Altaf Wani (Advisor)
144 p.
Biomedical Research

Recommended Citations

Citations

  • Racoma, I. O. (2013). Targeting Glioblastoma Survival Signaling: A Novel Mechanism of Action of Thymoquinone [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1369923513

    APA Style (7th edition)

  • Racoma, Ira. Targeting Glioblastoma Survival Signaling: A Novel Mechanism of Action of Thymoquinone. 2013. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1369923513.

    MLA Style (8th edition)

  • Racoma, Ira. "Targeting Glioblastoma Survival Signaling: A Novel Mechanism of Action of Thymoquinone." Doctoral dissertation, Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1369923513

    Chicago Manual of Style (17th edition)

osu1369923513
2,803
© 2013, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.