3‚ÄëBromopyruvate sensitizes human breast cancer cells to TRAIL‚Äëinduced apoptosis via the phosphorylated AMPK‚Äëmediated upregulation of DR5
Authors: Qiong Pan
Lanzhu Zhou
Li Wei
Song Zhang
Yuzhong Chen
Hao Liu
Xianfu Liu
Surong Zhao
Xiaojing Zhang
Yansong Chen
Qixiang Li
Journal: Oncology Reports (2018)
Discipline: CLINICAL MEDICINE
Keywords: breast cancer cells; TRAIL-induced apoptosis; death receptors; endoplasmic reticulum stress response; 3-Bromopyruvate
Affiliations: Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233000, P.R. China, Department of Gynecological Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233000, P.R. China, Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233000, P.R. China, Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China

Abstract:  Previous studies have indicated that the sensitivity of breast cancer cells to tumor necrosis factor‚Äërelated apoptosis‚Äëinducing ligand (TRAIL)‚Äëinduced apoptosis is associated with the expression of death receptors on the cell membrane. However, drug resistance limits the use of TRAIL in cancer therapy. Numerous studies have indicated that death receptors, which induce apoptosis, are upregulated by the endoplasmic reticulum (ER) stress response. 3‚ÄëBromopyruvate (3‚ÄëBP), an anticancer agent, inhibits cell growth and induces apoptosis through interfering with glycolysis. In the present study, it was demonstrated that 3‚ÄëBP synergistically sensitized breast cancer cells to TRAIL‚Äëinduced apoptosis via the upregulation of death receptor 5 (DR5). Furthermore, we found that the protein levels of glucose‚Äërelated protein 78 (GRP78) and CCAAT‚Äëenhancer‚Äëbinding protein homologous protein (CHOP) increased following treatment with 3‚ÄëBP. The expression of Bax (in MCF‚Ä? cells) and caspase‚Ä? (in MDA‚ÄëMB‚Ä?31 cells) increased following co‚Äëtreatment with 3‚ÄëBP and TRAIL, whereas the expression of the anti‚Äëapoptotic protein Bcl‚Ä? decreased. In order to investigate the molecular mechanism regulating this effect, the expression of adenosine monophosphate‚Äëactivated protein kinase (AMPK), activated by 3‚ÄëBP, was determined. It was demonstrated that phosphorylated‚ÄëAMPK was upregulated following treatment with 3‚ÄëBP. Notably, Compound C, an AMPK inhibitor, reversed the effects of 3‚ÄëBP. Finally, a synergistic antitumor effect of 3‚ÄëBP and TRAIL was observed in MCF‚Ä? cell xenografts in nude mice. In conclusion, these results indicated that 3‚ÄëBP sensitized breast cancer cells to TRAIL via the AMPK‚Äëmediated upregulation of DR5. 

Retracted: No

PubPeer comments:
 Figure 3A contains two WB bands which appear more similar than expected.  , 
 Thank you for your efforts to review my article. Due to our own lack of rigor, the protein expression of CHOP was incorrectly placed in the position of p-AMPK when the pictures were typeset. We did not notice this problem when we proofed the article. We checked the original data in this experiment. The expression trend of p-AMPK is consistent with the result of my article. Our experiment was repeated three times. The experimental results are reliable, and the in vivo experiments in the article have also verified the effects of drugs. Itu2019s my faults for any negligence in my wok, although it was unintentional mistake. This also warns me to be more rigorous in my future work. Thank you again for your correction. , 
  , 
 Corrigendum published, [17 January 2022] .  Following the publication of this article, an interested reader drew to the authors attention that the western blotting data shown in Fig. 3 on. p. 2439 contained apparent anomalies; first, the protein bands shown to represent the CHOP and pu2011AMPK experiments in Fig. 3A were strikingly similar. Secondly, the same data bands were inadvertently included in the figure to represent the GRP78 and Bax experiments for the MCFu20117 group. The authors have reu2011examined their original data and realized that this figure was assembled incorrectly (the CHOP and GRP78 data were inadvertently duplicated in the figure). The corrected version of Fig. 3, showing the correct data for the pu2011AMPK and Bax experiments for the MCFu20117 group in Fig. 3A, is shown on the next page. The authors sincerely apologize for the error that was introduced during the preparation of this figure, thank the Editor of *Oncology Reports* for granting them the opportunity to publish a Corrigendum, and are grateful to the reader for alerting them to this issue. The authors also regret any inconvenience that this mistake may have caused. ,