Response of human non-small-cell lung cancer cells to the influence of Wogonin with SGK1 dynamics.
A number of significant studies in the field of cell biology have revealed another pattern of intracellular signal transduction in which cells transmit information through the dynamics of key signaling molecules. Dynamical properties of p53 have been demonstrated to be the key factor in dictating cell fate, including cell cycle arrest, permanent cell cycle arrest, and cell death. Previous studies showed a negative feedback regulation pathway between SGK1 and p53, but the dynamics of SGK1 have never been reported before. Therefore, we used different dosing strategies of Wogonin to affect SGK1 dynamics and investigate its impact on cell response. Key factors, such as APAF1, BAX, GADD45A, p21, PML, and YPEL3, which are related to cell cycle arrest, senescence, and apoptosis, were measured at different time points after incubation with Wogonin. Western blot and quantitative reverse transcriptase-polymerase chain reaction analysis were used to examine protein and mRNA expression of these genes. In addition, we also used β-galactosidase staining and flow cytometric analysis to further verify the results. It was found that Wogonin inhibited cell viability and downregulated SGK1 protein levels; 20 μM Wogonin could induce non-small-cell lung cancer A549 cells into cell cycle arrest/senescence/apoptosis after 0.5/2/4 h, respectively; and SGK1 dynamics showed significant differences under different cell responses. Together, our findings showed that SGK1 protein dynamics can be an important part of intracellular signaling, directly influencing cellular response decisions.
Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
Guanglin
G
Shi
Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
Qian
Q
Wang
Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
Xiaoyu
X
Zhou
Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
Jun
J
Li
Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
Hua
H
Liu
Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
Jun
J
Gu
Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
Haiying
H
Wang
Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
Yi
Y
Wu
Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
Liang
L
Ding
Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
Songshi
S
Ni
Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
Zhiyuan
Z
Tang
D000072283:A549 Cells; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007700:Kinetics; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases; D000097642:GADD45 Proteins
D053477:Apoptotic Protease-Activating Factor 1; D018797:Cell Cycle Proteins; D044950:Flavanones; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D051028:bcl-2-Associated X Protein; D000099184:Serum-Glucocorticoid Regulated Kinases; C506592:APAF1 protein, human; C494826:BAX protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C085514:wogonin
NSCLC; SGK1; cell response; dynamic