title: Effect of cell cycle phase on the sensitivity of SAS cells to sonodynamic therapy using low-intensity ultrasound combined with 5-aminolevulinic acid in vitro.
abstract: Sonodynamic therapy (SDT) with 5-aminolevulinic acid (5-ALA) can effectively inhibit various types of tumor in vitro and in vivo. However, the association between the efficacy of SDT and the phase of the cell cycle remains to be elucidated. 5-ALA may generate different quantities of sonosensitizer, protoporphyrin IX (PpIX), in different phases of the cell cycle, which may result in differences in sensitivity to 5-ALA-induced SDT. The present study aimed to investigate the effect of the cell cycle on the susceptibility of SAS cells to SDT following synchronization to different cell cycle phases. These results indicates that the rates of cell death and apoptosis of the SAS cells in the S and G2/M phases were significantly higher following SDT, compared with those in the G1-phase cells and unsynchronized cells, with a corresponding increase in PpIX in the S and G2/M cells. In addition, the expression of caspase-3 increased, while that of B-cell lymphoma (Bcl)-2 decreased markedly in theS and G2/M cells following SDT. Cyclin A was also expressed at higher levels in the S and G2/M cells, compared with the G1-phase cells. SDT also caused a significant upregulation of cyclin A in all phases of the cell cycle, however this was most marked in the S and G2/M cells. It was hypothesized that high expression levels of cyclin A in the S and G2/M cells may promote the induction of caspase-3 and reduce the induction of Bcl-2 by SDT and, therefore, enhance apoptosis. Taken together, these data demonstrated that cells in The S and G2/M phases generate more intracellular PpIX, have higher levels of cyclin A and are, therefore, more sensitive to SDT-induced cytotoxicity. These findings indicate the potential novel approach to preventing the onset of cancer by combining cell-cycle regulators with SDT. This sequential combination therapy may be a simple and cost-effective way of enhancing the effects of SDT in clinical settings.
authors.affiliation: Department of Oral Maxillofacial Surgery, School of Stomatology, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Stomatology, the Fourth Clinical College, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Anatomy, Basic Medical Science College, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anatomy, Basic Medical Science College, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Laboratory of Sono‑ and Photo‑theranostic Technologies, Harbin Institute of Technology, Harbin, Heilongjiang 150080, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Laboratory of Sono‑ and Photo‑theranostic Technologies, Harbin Institute of Technology, Harbin, Heilongjiang 150080, P.R. China.
authors.forename: Wenwu
authors.initials: W
authors.lastname: Cao
authors.affiliation: Laboratory of Sono‑ and Photo‑theranostic Technologies, Harbin Institute of Technology, Harbin, Heilongjiang 150080, P.R. China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Oral Maxillofacial Surgery, School of Stomatology, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Jiao
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D001711:Biotransformation; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017319:Photosensitizing Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011524:Protoporphyrins / Q000096:biosynthesis; D011836:Radiation Tolerance; D015398:Signal Transduction; D014059:Tongue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D014464:Ultrasonic Therapy / Q000379:methods; D000069453:Ultrasonic Waves
chemical_list: C000595707:BCL2 protein, human; D019925:Cyclin A; D017319:Photosensitizing Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D053148:Caspase 3