rApoptin induces apoptosis in human breast cancer cells via phosphorylation of Nur77 and Akt
Authors: Jun Mao
Zhenhuan Hou
Lianhong Li
Ying Lu
Journal: Biochemical and Biophysical Research Communications (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Akt; Apoptosis; Breast cancer; Nur77; rApoptin.
Affiliations: Department of Pathology, Dalian Medical University, Dalian 116044, China., Department of Pathology, Dalian Medical University, Dalian 116044, China; Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian 116044, China; Teaching Laboratory of Morphology, Dalian Medical University, Dalian 116044, China., Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian 116044, China; Teaching Laboratory of Morphology, Dalian Medical University, Dalian 116044, China., Department of Pathology, Dalian Medical University, Dalian 116044, China; Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian 116044, China. Electronic address: .

Abstract:  Breast cancer is the leading cause of cancer incidence and cancer-related mortality among women and is becoming a major public health problem around the world. The current study aims to investigate the possible role and mechanism of recombinant Apoptin (rApoptin), a potential anticancer candidate that minimally impacts normal cells, in the breast cancer cell proliferation and apoptosis in vitro and in vivo. We found that rApoptin could effectively inhibit the proliferation and apoptosis in MCF-7 and MDA-MB-231 cells in vitro, which was further confirmed by flow cytometry analysis. Apoptin partially inhibited MCF-7 cell xenograft tumor development in vivo. Furthermore, we found via western blot that rApoptin-induced apoptosis in MCF-7 and MDA-MB-231 cells was associated with the phosphorylation of Nur77 (p-Nur77) and Akt (p-Akt). In addition, compared with the control groups, rApoptin-treated tissues showed significantly higher expression of Bax and Cyt c while Bcl-2 expression was decreased by rApoptin treatment. Together, our results are the first to demonstrate that rApoptin was able to effectively induce breast cancer cell apoptosis both in vitro and in vivo and that this activity could be regulated by the phosphorylation of Nur77 and Akt and the mitochondrial pathway. Our findings highlight the potential application of rApoptin as a breast cancer treatment. 

Retracted: No

PubPeer comments:
 This article is part of the special issue guest edited by a JUUL consultant, as described in the editorial introducing the special issue (1). The COI disclosure in the editorial says:  Through PinneyAssociates, Saul Shiffman provides consulting services on tobacco harm reduction on an exclusive basis to Juul Labs Inc. In that role, he acted as internal editor and coordinator for the papers in this special issue. Saul Shiffman is also a senior author of this paper. Indeed, Shiffman is an author (sometimes first or senior author) on 10 articles in the special issue (2-11). I note that Shiffman has claimed that he was  not an editor for this issue (12). Is that really the case? Shiffman and JUUL employee Erik Auguston signed the introductory editorial. Shiffman s COI disclosure in the introductory editorial says he was  internal editor and coordinator for the papers in this special issue. In each of the papers, there is a disclosure of the financial ties between the authors (including Shiffman) and JUUL. But how is the reader supposed to know that these articles went through a  special issue editorial process, supervised by Shiffman himself, in his role as a JUUL consultant? The American Journal of Health Behavior says that it adheres to COPE guidelines. COPE says that it can be appropriate for an editor to publish a study in their own journal,  provided every effort is made to minimise any bias in the review process by having another associate editor handle the peer review procedure independently of the editor (recognising that it would be impossible to remove bias completely), and the process is absolutely transparent (13). The process regarding this special issue was not transparent. Even if the manuscripts did go through the full review process, the disclosure of the editorial roles of Shiffman and Auguston should be present in every article in the special issue, not just the introductory editorial. It may (may) suffice for COPE that the sponsor of a special issue is disclosed once in the issue; in today s world where researchers consume individual articles, disclosure of issue sponsorship should happen at the article level too. 1. Shiffman S, Augustson EM. Introduction to the Special Issue on JUUL Use. American Journal of Health Behavior. 2021 May 1;45(3):397u2013401. 2. Shiffman S, Holt NM. Smoking Trajectories of Adult Never Smokers 12 Months after First Purchase of a JUUL Starter Kit. Am J Health Behav. 2021 May 1;45(3):527u201345. 3. Shiffman S, Goldenson NI, Hatcher C, Augustson EM. Changes in Dependence as Smokers Switch from Cigarettes to JUUL in Two Nicotine Concentrations. Am J Health Behav. 2021 May 1;45(3):563u201375. 4. Selya AS, Shiffman S, Greenberg M, Augustson EM. Dual Use of Cigarettes and JUUL: Trajectory and Cigarette Consumption. Am J Health Behav. 2021 May 1;45(3):464u201385. 5. Prakash S, Xu Y, Goldenson NI, Wissmann R, Gougelet R, Shiffman S. Transitions in Smoking among Adults Newly Purchasing the JUUL System. Am J Health Behav. 2021 May 1;45(3):546u201362. 6. Prakash S, Hatcher C, Shiffman S. Prevalence of ENDS and JUUL Use, by Smoking Status, in National Samples of Young Adults and Older Adults in the U.S. Am J Health Behav. 2021 May 1;45(3):402u201318. 7. Le GM, Holt NM, Goldenson NI, Smith LC, Hatcher C, Shiffman S, et al. Cigarette Smoking Trajectories in Adult Former Smokers Using the JUUL System. Am J Health Behav. 2021 May 1;45(3):505u201326. 8. Kim S, Shiffman S, Le GM. Switching away from Cigarette Smoking with JUUL: Populations of Special Interest. Am J Health Behav. 2021 May 1;45(3):486u2013504. 9. Goldenson NI, Shiffman S, Hatcher C, Lamichhane D, Gaggar A, Le GM, et al. Switching away from Cigarettes across 12 Months among Adult Smokers Purchasing the JUUL System. Am J Health Behav. 2021 May 1;45(3):443u201363. 10. Chen T, Prakash S, Zion A, Joselow J, Shiffman S, Kasmer PD. Improving Retailer Compliance for Tobacco Purchases: Pilot Study Findings. Am J Health Behav. 2021 May 1;45(3):576u201387. 11. Shiffman S, Sembower MA, Augustson EM, Goldenson NI, Haseen F, McKeganey NP, et al. The Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study: Methods and Analysis of Loss-to-Follow-up. Am J Health Behav. 2021 May 1;45(3):419u201342. 12. Re: Academic journal is criticised for publishing special issue funded by tobacco industry. 2021 Jul 14 [cited 2021 Jul 15];n1247. Available from: https: www.bmj.com content 373 bmj.n1247 rr-0 13. Editor as author in own journal | COPE: Committee on Publication Ethics [Internet]. [cited 2021 Jul 15]. Available from: https: publicationethics.org case editor-author-own-journal , 
 #1 As the post is about my role in these publications, please allow me to clarify the facts and dispel some misconceptions about my role as u201cinternal editoru201d (the wording was unfortunate, and contributed to this misconception). My role was to help coordinate development of the papers among the authors by, for example, promoting the use of common terminology and definitions, and similar modes of analysis where appropriate. I was not involved in the journalu2019s independent editorial process: I did not make reviewer assignments, and I did not make decisions about accepting manuscripts for publication, those decisions were made solely by the journalu2019s editor-in-chief, Dr. Glover. I trust this responds to the concerns in your post. Please reach out if you have additional questions. Saul Shiffman, PhD Senior Scientific Advisor, Pinney Associates (consultants to JUUL) Professor of Psychology, University of Pittsburgh ,