title: Inhibition of γ-secretase by retinoic acid chalcone (RAC) induces G2/M arrest and triggers apoptosis in renal cell carcinoma.
abstract: The present study was devised to investigate the effect of RAC on inhibition of cell proliferation and apoptosis of renal carcinoma cells. MTT assay and flow cytometry analysis were used to determine cell proliferation and apoptosis along with cell cycle examination. Western blot analysis and immunohistochemistry were used for the detection of expression levels of Notch1 and Jagged1 in renal cell carcinoma (RCC) and normal kidney tissues. The results revealed a significant inhibition of cell proliferation, G2/M phase cell cycle arrest and cell apoptosis at 30 μM concentration of RAC after 72 h. In ACHN and 769-P cells, the population in G2/M phase was increased to 45.27, and 54.23% respectively on treatment with 30 μM RAC for 72 h. In 769-P and ACHN renal carcinoma cells treatment with 30 μM RAC caused 69.71 and 59.27% of the cells to undergo apoptosis compared to 5.23 and 4.93% respectively in control cells. The positive staining rates of Notch1 and Jagged1 in renal carcinoma tissues were 95.3 and 93.0% compared to normal kidney tissues 36.4 and 42.4% respectively. Treatment of renal carcinoma tissues caused a significant decrease in staining rates of Notch1 and Jagged1 after 96 h. Thus RAC can be a potent agent in the treatment of renal cell carcinoma.
authors.affiliation: Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University Changchun 130033, Jilin, China.
authors.forename: Qing-Chun
authors.initials: QC
authors.lastname: Li
authors.affiliation: Center of Physical Examination, China-Japan Union Hospital of Jilin University Changchun 130033, Jilin, China.
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Li
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences Changchun 130022, Jilin, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Liu
authors.affiliation: Center of Physical Examination, China-Japan Union Hospital of Jilin University Changchun 130033, Jilin, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Center of Physical Examination, China-Japan Union Hospital of Jilin University Changchun 130033, Jilin, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Jilin Institute for Drug Control Changchun 130033, Jilin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D051881:Receptor, Notch1 / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014212:Tretinoin / Q000031:analogs & derivatives / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D047188:Chalcones; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; D014212:Tretinoin; D053829:Amyloid Precursor Protein Secretases
keywords: Jagged1; Notch1; Renal cell carcinoma; apoptosis