FV-429 Induced Apoptosis Through ROS-Mediated ERK2 Nuclear Translocation and p53 Activation in Gastric Cancer Cells
Authors: Qinsheng Dai
Zhiyu Li
Libin Wei
Yuxin Zhou
Boyang Yu
Qinglong Guo
Na Lu
Haiwei Zhang
Journal: Journal of cellular biochemistry (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: EXTRACELLULAR REGULATED KINASE; NUCLEAR TRANSLOCATION; REACTIVE OXYGEN SPECIES; p53.
Affiliations: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, JiangSu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, P.R. China., Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, P.R. China.

Abstract:  Following our previous finding which revealed that FV-429 induces apoptosis in human hepatocellular carcinoma HepG2 cells, in this study, we found that FV-429 could also induce apoptosis in human gastric cancer cells. Firstly, FV-429 inhibited the viability of BGC-823 and MGC-803 cells with IC50 values in the range of 38.10 ± 6.28 and 31.53 ± 6.84 µM for 24 h treatment by MTT-assay. Secondly, FV-429 induced apoptosis in BGC-823 and MGC-803 cells through the mitochondrial-mediated pathway, showing an increase in Bax/Bcl-2 ratios, and caspase-9 activation, without change in caspase-8. Further research revealed that the mitogen-activated protein kinases, including c-Jun N-terminal kinase, extracellular regulated kinase, and p38 mitogen-activated protein kinase, could be activated by FV-429-induced high level ROS. Moreover, FV-429 also promoted the ERK2 nuclear translocation, resulting in the co-translocation of p53 to the nucleus and increased transcription of p53-regulated proapoptotic genes. FV-429 significantly inhibited the nude mice xenograft tumors growth of BGC-823 or MGC-803 cells in vivo. 

Retracted: No

PubPeer comments:
 Figure 4B: Two cases of data duplications: ![file] , 
 Comparing Figs 5D, 6A. ![file] Same control band, different conditions. , 
 #1  Figure 4B: Two cases of data duplications: I have concerns about Lane 5 in four bands of Fig 4B, not just two. ![file] At right, I ve adjusted the lightness contrast of the blobs of interest to emphasise their internal features. , 
 #3 Comparing Fig 4B *[right]* with Fig 5A *[left]* from [Zhou et al (2013)] . ![file] The two procaspase-8 bands are of special interest. Shown at bottom with some rescaling. , 
 At left, Figures 6E and 6F from [Zhou et al (2013)] . Two points of interest here. First, the Actin band from 6F reappears in *[at right]* the present Fig 4E. ![file] Second, the histone band from 6E seems to be the same, apart from a 180-deg rotation. , 
 Figures 6B and 6I. Could the authors check whether the indicated bands represent Histone expression in MGC-803 cells, or ERK-2 in BGC-823 cells? ![file] I also have concerns about the Cytosol beta-Actin band for BGC-823 cells, in Fig 5B *[at bottom]*. , 
 Figure 2D, MGC-803 Wogonin panel. I have concerns. ![file] , 
 Corrected [14 October 2019] :  In the original publication, the resolution and quality for some WB bands in Figure 4B are low, which caused some confusing. We would like to replace it with high quality WB bands that are the another result in three times repeated experiments.  Figure 4B in published paper: ![]  Correct Figure 4B with high quality bands: ![] , 
 #8  Correct Figure 4B with high quality bands - this strikes me as a misnomer. The main difference between the original and the new 4B is that the Bcl-2 and Procaspase-9 bands were replaced while other bands remained the same. ![file] Was this what the authors meant by  high quality WB bands that are the another result in three times repeated experiments ? They seem to be saying that Fig 4B now a composite consisting of alternating bands from different experiments. , 
 #8, #9 based on yours and inputs from @houndcl @Thatsregrettab1, the higher quality replacement figure from the authors include the following: ![](http: i.imgur.com iRiasdh.jpg) , 
 #9 Thanks for updating the high quality WB bands. Unfortunately, I still have concerns. ![] ,