Histone Deacetylase Inhibitor Trichostatin a Promotes the Apoptosis of Osteosarcoma Cells through p53 Signaling Pathway Activation
Authors: Yong Wang
Qian Gao
Xiaozhou Liu
Jianning Zhao
Jiewen Jin
Zhantao Deng
Haidong Xu
Journal: International Journal of Biological Sciences (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: HDAC; Trichostatin A; apoptosis; osteosarcoma; p53.
Affiliations: Department of Orthopedics, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.; Center for Translational Medicine, Nanjing University Medical School, Nanjing, Jiangsu, PR China.; Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, PR China., Department of Orthopedics, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China., Center for Translational Medicine, Nanjing University Medical School, Nanjing, Jiangsu, PR China.; Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, PR China.

Abstract:  Purpose: The purpose of this study was to investigate the profile of histone deacetylase (HDAC) activity and expression in osteosarcoma cells and tissues from osteosarcoma patients and to examine the mechanism by which a histone deacetylase (HDAC) inhibitor, Trichostatin A (TSA), promotes the apoptosis of osteosarcoma cells. Methods: HDAC activity and histone acetyltransferase (HAT) activity were determined in nuclear extracts of MG63 cells, hFOB 1.19 cells and tissues from 6 patients with primary osteosarcoma. The protein expression of Class I HDACs (1, 2, 3 and 8) and the activation of the p53 signaling pathway were examined by Western blot. Cell growth and apoptosis were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) assay and flow cytometry, respectively. Results: Nuclear HDAC activity and class I HDAC expression were significantly higher in MG63 cells than in hFOB 1.19 cells, and a similar trend was observed in the human osteosarcoma tissues compared with the paired adjacent non-cancerous tissues. TSA significantly inhibited the growth of MG63 cells and promoted apoptosis in a dose-dependent manner through p53 signaling pathway activation. Conclusion: Class I HDACs play a central role in the pathogenesis of osteosarcoma, and HDAC inhibitors may thus have promise as new therapeutic agents against osteosarcoma. 

Retracted: No

PubPeer comments:
 **Figure 5D, duplication with alteration was found. This type of reproduction is difficult to interpret as image misuse** ![file] **There is an obvious duplication problem in the red box in the two pictures. It is worth noting that when you look carefully, you will find that the distribution of points in the left red box is completely consistent with that in the right box. The author only deleted or added some points in the right box (shown in red circle)** ![file] ![file] , 
 #1 **More repeated motifs were detected by an image plagiarism detection software**. ![file] , 
 There is also the consistency problem of large-area lattice distribution between Fig. 4B and Fig. 5D, and careful observation can find that there are artificial erasure of individual points or stretching of local repeating units. ![file] ,