A novel triterpenoid isolated from the root bark of Ailanthus excelsa Roxb (Tree of Heaven), AECHL-1 as a potential anti-cancer agent
Authors: Shri Hari Mishra
Manish S Lavhale
Sandhya L Sitasawad
Santosh Kumar
Journal: PloS one (2009)
Discipline: Multidisciplinary
Keywords: Ailanthus excelsa; AECHL-1; anti-cancer activity; cell proliferation; tumor suppressor proteins
Affiliations: Pharmacy Department, Faculty of Technology and Engineering, The MS University of Baroda, Vadodara, Gujarat, India.

Abstract:  Background: We report here the isolation and characterization of a new compound Ailanthus excelsa chloroform extract-1 (AECHL-1) (C(29)H(36)O(10); molecular weight 543.8) from the root bark of Ailanthus excelsa Roxb. The compound possesses anti-cancer activity against a variety of cancer cell lines of different origin. Principal findings: AECHL-1 treatment for 12 to 48 hr inhibited cell proliferation and induced death in B16F10, MDA-MB-231, MCF-7, and PC3 cells with minimum growth inhibition in normal HEK 293. The antitumor effect of AECHL-1 was comparable with that of the conventional antitumor drugs paclitaxel and cisplatin. AECHL-1-induced growth inhibition was associated with S/G(2)-M arrests in MDA-MB-231, MCF-7, and PC3 cells and a G(1) arrest in B16F10 cells. We observed microtubule disruption in MCF-7 cells treated with AECHL-1 in vitro. Compared with control, subcutaneous injection of AECHL-1 to the sites of tumor of mouse melanoma B16F10 implanted in C57BL/6 mice and human breast cancer MCF-7 cells in athymic nude mice resulted in significant decrease in tumor volume. In B16F10 tumors, AECHL-1 at 50 microg/mouse/day dose for 15 days resulted in increased expression of tumor suppressor proteins P53/p21, reduction in the expression of the oncogene c-Myc, and downregulation of cyclin D1 and cdk4. Additionally, AECHL-1 treatment resulted in the phosphorylation of p53 at serine 15 in B16F10 tumors, which seems to exhibit p53-dependent growth inhibitory responses. Conclusions: The present data demonstrate the activity of a triterpenoid AECHL-1 which possess a broad spectrum of activity against cancer cells. We propose here that AECHL-1 is a futuristic anti-cancer drug whose therapeutic potential needs to be widely explored for chemotherapy against cancer. 

Retracted: Yes

PubPeer comments:
 The unethical xenografts in Fig. 6C of this 2009 paper are not just yuge, they are also a tad necrotic. Having seem them, I now canu2019t get u201cBad Moon Risingu201d out of my head? ![image] Even so, these u201cBad Xenografts Risingu201d might have lost out to Nature Publishing Groupu2019s more recent offerings on size (2011) here https: pubpeer.com publications 86A05A1191BCC54266244DB3839DAA and necrosis (2015) here https: pubpeer.com publications A7E4AE815775161947341A3C63FC52 Nobody messes with the Nature Publishing Group: Everyday, in every way, theyu2019re getting bigger and bigger and better. Onwards and upwards! Ethical guidelines for Xenografts are available here https: www.ncbi.nlm.nih.gov pmc articles PMC2883160 Albeit from 2010, so a year too late to have intervened on behalf of these particular naturist meeces. Were no other guidelines ever published before 2009? , 
 I thank PLOS One for responding to my concerns by conducting an investigation and then retracting this paper for unethical laboratory animal husbandry. ![image] , 
 2020 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0231249 After this article [1] was published, concerns were raised about the mouse tumor sizes reported in Fig 6. The figure reports tumor volume in percent growth compared to baseline, but the authors provided actual tumor size data in post-publication discussions. These data confirmed that tumor sizes up to 13.12 cm3 were observed in the study. The authors commented that per their observations mouse mobility was not hindered during the experiments, and that extra care was taken to make food easily available. They noted that they observed animals twice daily for morbidity and mortality, and animals were assessed once daily (after treatment) for signs of behavioral changes, food and water consumption, body weight, illness, and reactions to treatment. Per the study protocol, animals were to be euthanized if they were determined to be in overt pain and or distress, if death seemed imminent, or if they appeared beyond the point where recovery appears possible. The authors provided a copy of an ethics approval document per the journalu2019s request, and none of the articleu2019s authors were included in the list of individuals authorized to conduct procedures under the approved proposal. A member of PLOS ONEu2019s Animal Research Advisory Group assessed the article and the authorsu2019 comments and confirmed that the tumor sizes reported far exceed community standards for humane endpoint limits in mouse tumor studies. The advisor noted that the tumor results present a significant animal welfare and ethical concern. In light of the above concerns, the PLOS ONE Editors retract this article. The editors regret that these concerns were not addressed at the time of the original review process. The articleu2019s authors either could not be reached or did not respond directly to the retraction notification. Reference 1.Lavhale MS, Kumar S, Mishra SH, Sitasawad SL (2009) A Novel Triterpenoid Isolated from the Root Bark of Ailanthus excelsa Roxb (Tree of Heaven), AECHL-1 as a Potential Anti-Cancer Agent. PLoS ONE 4(4): e5365. https: doi.org 10.1371 journal.pone.0005365 ,