(6)-Gingerolinduced myeloid leukemia cell death is initiated by reactive oxygen species and activation of miR-27b expression
Authors: Rachana Trivedi
Rakesh Maurya
Namrata Rastogi
Preety Dixit
Akanksha Singh
Shivali Duggal
Sarika Singh
Durga Prasad Mishra
Rishi Kumar Gara
M L B Bhatt
Journal: Free Radical Biology and Medicine (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: (6)-Gingerol; Apoptosis; DNA damage; Free radicals; G2/M arrest
Affiliations: Endocrinology Division, Central Drug Research Institute, Uttar Pradesh 226021, India., Medicinal and Process Chemistry Division, Central Drug Research Institute, Uttar Pradesh 226021, India., Department of Radiotherapy, CSM Medical University, Lucknow, Uttar Pradesh 226003, India., Toxicology Division, Central Drug Research Institute, Lucknow, Uttar Pradesh 226001, India., Endocrinology Division, Central Drug Research Institute, Uttar Pradesh 226021, India. Electronic address: .

Abstract:  The natural polyphenolic alkanone (6)-gingerol (6G) has established anti-inflammatory and antitumoral properties. However, its precise mechanism of action in myeloid leukemia cells is unclear. In this study, we investigated the effects of 6G on myeloid leukemia cells in vitro and in vivo. The results of this study showed that 6G inhibited proliferation of myeloid leukemia cell lines and primary myeloid leukemia cells while sparing the normal peripheral blood mononuclear cells, in a concentration- and time-dependent manner. Mechanistic studies using U937 and K562 cell lines revealed that 6G treatment induced reactive oxygen species (ROS) generation by inhibiting mitochondrial respiratory complex I (MRC I), which in turn increased the expression of the oxidative stress response-associated microRNA miR-27b and DNA damage. Elevated miR-27b expression inhibited PPARγ, with subsequent inhibition of the inflammatory cytokine gene expression associated with the oncogenic NF-κB pathway, whereas the increased DNA damage led to G2/M cell cycle arrest. The 6G induced effects were abolished in the presence of anti-miR-27b or the ROS scavenger N-acetylcysteine. In addition, the results of the in vivo xenograft experiments in mice indicated that 6G treatment inhibited tumor cell proliferation and induced apoptosis, in agreement with the in vitro studies. Our data provide new evidence that 6G-induced myeloid leukemia cell death is initiated by reactive oxygen species and mediated through an increase in miR-27b expression and DNA damage. The dual induction of increased miR-27b expression and DNA damage-associated cell cycle arrest by 6G may have implications for myeloid leukemia treatment. 

Retracted: No

PubPeer comments:
 Two different cells and same figure ![file] , 
 Dear Pubpeer members, we are thankful to you for bringing this error in the Figure 3, Panel B. to our notice. The control PBMC image has been mistakenly pasted in the U937 panel due to inadvertent error in sorting figures for analysis having single cell images through the CASPlab.com program and the mistake is deeply regretted. Another fact to consider is that both the images are for control panel. Albeit the reported error do not affect the final outcome of the experiment or the study as we have also shown the other evidence for the same data with pH2AX staining (Panel A ), Cell cycle analysis (Panel C ) and western blotting (Panel D) in this Figure. ![file] The correct image is shown herewith. Therefore the indicated error has no bearing on the conclusions made in the study. However, the authors regret this inadvertent error. Regards, Namrata Rastogi ,