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Low-Intensity Pulsed Ultrasound-Generated Singlet Oxygen Induces Telomere Damage Leading to Glioma Stem Cell Awakening From Quiescence
- Source :
- iScience, Vol 25, Iss 1, Pp 103558-(2022), iScience
- Publication Year :
- 2021
- Publisher :
- Research Square Platform LLC, 2021.
-
Abstract
- Summary Cancer stem cells, quiescent and drug resistant, have become a therapeutic target. Unlike high-intensity focused ultrasound directly killing tumor, low-intensity pulsed ultrasound (LIPUS), a new noninvasive physical device, promotes pluripotent stem cell differentiation and is primarily applied in tissue engineering but rarely in oncotherapy. We explored the effect and mechanism of LIPUS on glioma stem cell (GSC) expulsion from quiescence. Here, we observed that LIPUS led to attenuated expression of GSC biomarkers, promoted GSC escape from G0 quiescence, and significantly weakened the Wnt and Hh pathways. Of note, LIPUS transferred sonomechanical energy into cytochrome c and B5 proteins, which converted oxygen molecules into singlet oxygen, triggering telomere crisis. The in vivo and in vitro results confirmed that LIPUS enhanced the GSC sensitivity to temozolomide. These results demonstrated that LIPUS “waked up” GSCs to improve their sensitivity to chemotherapy, and importantly, we confirmed the direct targeted proteins of LIPUS in GSCs.<br />Graphical abstract<br />Highlights • LIPUS “waked quiescent GSCs up” and enhanced the sensitivity of temozolomide • LIPUS-generated singlet oxygen damaged telomeres, reducing GSCs stemness • Cytochrome B5 and c are targets for LIUPS energy transfer<br />Medical device; Cell biology; Stem cells research; Cancer
- Subjects :
- chemistry.chemical_classification
Cell biology
endocrine system
Reactive oxygen species
Multidisciplinary
Chemistry
Science
Wnt signaling pathway
Low-intensity pulsed ultrasound
medicine.disease
Article
Telomere
Stem cells research
Cancer stem cell
Glioma
medicine
Stem cell
Induced pluripotent stem cell
Medical device
Cancer
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- iScience, Vol 25, Iss 1, Pp 103558-(2022), iScience
- Accession number :
- edsair.doi.dedup.....d3d5310fad6a31848b871a62b44ad5d5