Glioma stem-like cells are less susceptible than glioma cells to sonodynamic therapy with photofrin.

Abstract

Despite remarkable progress in diagnosis and treatment, malignant glioma, a highly lethal cancer of the central nervous system, remains incurable. Although glioma stem-like cells (GSCs) represent a relatively small fraction of the cells in malignant glioma, they can proliferate and self renew extensively, being crucial for tumor recurrence. Cancer treatment by sonodynamic therapy (SDT) chiefly depends on antitumor effects of reactive oxygen species (ROS) generated from a sonosensitizer activated by ultrasound. Although SDT effectively kills glioma cells, its efficiency against GSCs is not established. We attempted to compare the susceptibility of GSCs to SDT, using Photofrin, a porphyrin-derivative photosensitizer, with that of glioma cells. Cell viability and apoptosis assays showed that SDT damaged both GSCs and U251 glioma cells, but GSCs were significantly less susceptible to SDT (p < 0.01). To elucidate the mechanism of the antitumor effects of SDT, we evaluated intracellular ROS production and Photofrin uptake: ROS production and Photofrin content were significantly lower (p < 0.01) in GSCs than in U251 glioma cells. Thus, cellular differences in sonosensitizer uptake and ROS production influence the antitumor effects of SDT. Furthermore, the resistance of GSCs may be caused by decreased sonosensitizer uptake due to ABCG2 overexpression.

• Authors: Zhong-Ye Xu, Xiao-Qing Li, Song Chen, Yuan Cheng, Jin-Mu Deng, Zhi-Gang Wang
• Journal: Technology in cancer research & treatment (Technol Cancer Res Treat) Vol. 11 Issue 6 Pg. 615-23 (Dec 2012) ISSN: 1533-0338 [Electronic] United States
• PMID: 22775340 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Antineoplastic Agents
• Neoplasm Proteins
• Reactive Oxygen Species
• Dihematoporphyrin Ether

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (metabolism)
• Antineoplastic Agents (metabolism, pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Dihematoporphyrin Ether (metabolism, pharmacology)
• Glioma (drug therapy, metabolism)
• Humans
• Neoplasm Proteins (metabolism)
• Neoplastic Stem Cells (drug effects, metabolism)
• Reactive Oxygen Species (metabolism)
• Sound
• Spheroids, Cellular
• Tumor Cells, Cultured