Journal ArticleDOI
The induction of autophagy by γ-radiation contributes to the radioresistance of glioma stem cells
Stephanie L. Lomonaco,Susan Finniss,Cunli Xiang,Ana C. deCarvalho,Felix Umansky,Steven N. Kalkanis,Tom Mikkelsen,Chaya Brodie,Chaya Brodie +8 more
TLDR
Results indicate that the induction of autophagy contributes to the radioresistance of these cells and Autophagy inhibitors may be employed to increase the sensitivity of CD133+ GSCs to γ‐radiation.Abstract:
Malignant gliomas are characterized by a short median survival which is largely impacted by the resistance of these tumors tochemo- and radiotherapy. Recent studies suggest that a small subpopulation of cancer stem cells, which are highly resistant to gamma-radiation, has the capacity to repopulate the tumors and contribute to their malignant progression. gamma-radiation activates the process of autophagy and inhibition of this process increases the radiosensitivity of glioma cells; however, the role of autophagy in the resistance of glioma stem cells (GSCs) to radiation has not been yet reported. In this study we examined the induction of autophagy by gamma-radiation in CD133+ GSCs. Irradiation of CD133+ cells induced autophagy within 24-48 hr and slightly decreased the viability of the cells. gamma-radiation induced a larger degree of autophagy in the CD133+ cells as compared with CD133- cells and the CD133+ cells expressed higher levels of the autophagy-related proteins LC3, ATG5 and ATG12. The autophagy inhibitor bafilomycin A1 and silencing of ATG5 and beclin1 sensitized the CD133+ cells to gamma-radiation and significantly decreased the viability of the irradiated cells and their ability to form neurospheres. Collectively, these results indicate that the induction of autophagy contributes to the radioresistance of these cells and autophagy inhibitors may be employed to increase the sensitivity of CD133+ GSCs to gamma-radiation.read more
Citations
More filters
Journal ArticleDOI
Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury
TL;DR: The role of mitochondria in the delayed outcomes of ionization radiation is discussed, and different types of radiation vary in their linear energy transfer (LET) properties, and their effects on various aspects of mitochondrial physiology are discussed.
Journal ArticleDOI
Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma
Reason Wilken,Mysore S. Veena,Mysore S. Veena,Marilene B. Wang,Marilene B. Wang,Eri S. Srivatsan,Eri S. Srivatsan +6 more
TL;DR: An overview of the current in vitro and in vivo data supporting its therapeutic activity in head and neck cancer as well as some of the challenges concerning its development as an adjuvant chemotherapeutic agent are presented.
Journal ArticleDOI
Autophagy and Cancer Therapy
Paola Maycotte,Andrew Thorburn +1 more
TL;DR: Recent research related to autophagy and cancer therapy is discussed with a focus on how these processes may be manipulated to improve cancer therapy.
iArc monogrAphs on the evAluAtion oF cArcinogenic risks to humAns
TL;DR: PReVIously ClAssIfIed by IARC As “CARCInogenIC to humAns (gRoup 1)” And wAs deVeloped by sIx sepARAte woRkIng gRoups: phARmACeutICAls; bIologICAl Agents; ARsenIC, metAls, fIbRes, And dusts; RAdIAtIon; peRsonAl
Journal ArticleDOI
Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation
Su Yeon Lee,Eui Kyong Jeong,Min Kyung Ju,Hyun Min Jeon,Min Young Kim,Cho Hee Kim,Hye Gyeong Park,Song Iy Han,Ho Sung Kang +8 more
TL;DR: How IR- induced EMT/CSC/oncogenic metabolism may promote resistance to radiotherapy is discussed and efforts to develop therapeutic approaches to eliminate these IR-induced adverse effects are reviewed.
References
More filters
Journal ArticleDOI
Identification of human brain tumour initiating cells
Sheila K. Singh,Cynthia Hawkins,Ian D. Clarke,Jeremy A. Squire,Jane Bayani,Takuichiro Hide,R. Mark Henkelman,Michael D. Cusimano,Peter B. Dirks +8 more
TL;DR: The development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo gives strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.
Journal ArticleDOI
Glioma stem cells promote radioresistance by preferential activation of the DNA damage response
Shideng Bao,Qiulian Wu,Roger E. McLendon,Yueling Hao,Qing Ming Shi,Anita B. Hjelmeland,Mark W. Dewhirst,Darell D. Bigner,Jeremy N. Rich +8 more
TL;DR: This work shows that cancer stem cells contribute to glioma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity, and suggests that CD133-positive tumour cells could be the source of tumour recurrence after radiation.
Journal Article
Identification of a Cancer Stem Cell in Human Brain Tumors
Sheila K. Singh,Ian D. Clarke,Mizuhiko Terasaki,Victoria E. Bonn,Cynthia Hawkins,Jeremy A. Squire,Peter B. Dirks +6 more
TL;DR: The identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation is reported.
Journal ArticleDOI
Autophagy as a Regulated Pathway of Cellular Degradation
Daniel J. Klionsky,Scott D. Emr +1 more
TL;DR: The core protein machinery that is necessary to drive formation and consumption of intermediates in the macroautophagy pathway includes a ubiquitin-like protein conjugation system and a protein complex that directs membrane docking and fusion at the lysosome or vacuole.
Journal ArticleDOI
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Xueping Qu,Jie Yu,Govind Bhagat,Norihiko Furuya,Hanina Hibshoosh,Andrea B. Troxel,Jeffrey M. Rosen,Eeva-Liisa Eskelinen,Noboru Mizushima,Yoshinori Ohsumi,Giorgio Cattoretti,Beth Levine +11 more
TL;DR: It is shown that heterozygous disruption of beclin 1 increases the frequency of spontaneous malignancies and accelerates the development of hepatitis B virus-induced premalignant lesions, providing genetic evidence that autophagy is a novel mechanism of cell-growth control and tumor suppression.