An MD Anderson Cancer Center researcher who has been under investigation by the institution for at least several years has had seven papers retracted from a single journal.
Bharat Aggarwal told us in 2012 that MD Anderson was investigating his work, but in 2013 threatened to sue us for reporting on the case. Aggarwal is no longer listed in the MD Anderson directory, and an email to him there bounced.
This week, Biochemical Pharmacology retracted seven studies of which he is the only common author, noting the “data integrity has become questionable.” The papers have been cited a total of more than 500 times, according to Thomson Scientific’s Web of Knowledge; one has been designated as “highly cited.” Here are the seven retractions:
“Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines” (published in 2007, cited 96 times):
This article has been retracted at the request of the Editor.
The four images of the ß-actin band in Fig. 4B were reused to represent different experimental conditions in Fig. 3E.
The article has been retracted because the data integrity has become questionable.
“Thymoquinone poly(lactide-co-glycolide) nanoparticles exhibit enhanced anti-proliferative, anti-inflammatory, and chemosensitization potential” (published in 2010, cited 41 times):
This article has been retracted at the request of the Editor.
An image in Fig. 6 was reused to represent two different experimental conditions: images of paclitaxel alone (“Paclitaxel”) and of thymoquinone plus paclitaxel (“TQ + Paclitaxel”) are manipulations of the same image.
The article has been retracted because the data integrity has become questionable.
“Curcumin potentiates the antitumor effects of gemcitabine in an orthotopic model of human bladder cancer through suppression of proliferative and angiogenic biomarkers” (published in 2010, cited 48 times):
This article has been retracted at the request of the Editor.
In Fig. 5A different intensities of the same image were used to represent different experimental conditions: the extent of cell death of TUNEL/Vehicle (left image) and the extent of cell death of TUNEL/Curcumin (2nd image from the left).
The article has been retracted because the data integrity has become questionable.
“Suppression of pro-inflammatory and proliferative pathways by diferuloylmethane (curcumin) and its analogues dibenzoylmethane, dibenzoylpropane, and dibenzylideneacetone: Role of Michael acceptors and Michael donors” (published in 2011, cited 24 times):
This article has been retracted at the request of the Editor.
In Figs. 6B and 6E the images of ß-actin were reused to represent different experimental conditions: as the loading control for a concentration dependency study of dibenzoylmethane (DBM; Fig. 6B) and as the loading control for a concentration dependency study of dibenzoylpropane (DBP; Fig. 6E).
The article has been retracted because the data integrity has become questionable.
“Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo” (published in 2010, cited 236 times, earning a “highly cited” designation):
This article has been retracted at the request of the Editor.
Images from Fig. 2A were reused in Fig. 5A of Ref. [1] to represent different experimental conditions: four of the control images of cellular uptake of curcumin shown in Fig. 2A (45, 60, 120 and 180 min) are also shown in Fig. 5A (45, 60, 120 and 180 min) of Ref. [1].
The article has been retracted because the data integrity has become questionable.
References
[1] V.R. Yadav, S. Prasad, R. Kannappan, J. Ravindran, M.M. Chaturvedi, L. Vaahtera, J. Parkkinen, B.B. Aggarwal
Cyclodextrin-complexed curcumin exhibits anti-inflammatory and antiproliferative activities superior to those of curcumin through higher cellular uptake
Biochem. Pharmacol., 80 (2010), pp. 1021–1032 http://dx.doi.org/10.1016/j.bcp.2010.06.022
“Cyclodextrin-complexed curcumin exhibits anti-inflammatory and antiproliferative activities superior to those of curcumin through higher cellular uptake” (published in 2010, cited 68 times):
This article has been retracted at the request of the Editor.
Fig. 1A (3rd lane; CDC) was manipulated by replicating an image of a control lane from Fig. 1C (left lane) to represent different experimental conditions.
Fig. 1D, of nuclei isolated from cells in medium (“Nuclei/Medium”), was reused in Fig. 1G in reference [1], to represent different experimental conditions (nuclei of cells treated with γ-T3; “Nuclei/γ-T3”).
Images in Fig. 5A were reused to represent different experimental conditions: curcumin uptake by KBM-5 cells treated with curcumin alone at 30 min, and curcumin uptake by KBM-5 cells treated with cyclodextrin-complexed curcumin (CDC) at 45 min.
Images from Fig. 5A were reused in Fig. 2A of Ref. [2] to represent different experimental conditions: four of the control images of cellular uptake of curcumin shown in Fig. 5A (45, 60, 120 and 180 min) are also shown in Fig. 2A (45, 60, 120 and 180 min) of Ref. [2].
The article has been retracted because the data integrity has become questionable.
References
[1] R. Kannappan, V.R. Yadav, B.B. Aggarwal
γ-Tocotrienol but not γ-tocopherol blocks STAT3 cell signaling pathway through induction of protein-tyrosine phosphatase SHP-1 and sensitizes tumor cells to chemotherapeutic agents
J. Biol. Chem., 285 (2010), pp. 33520–33528 http://dx.doi.org/10.1074/jbc.M110.158378[2]P. Anand, H.B. Nair, B. Sung, A.B. Kunnumakkara, V.R. Yadav, R.R. Tekmal, B.B. Aggarwal
Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo
Biochem. Pharmacol., 79 (2010), pp. 330–338 http://dx.doi.org/10.1016/j.bcp.2009.09.003
“Triptolide, histone acetyltransferase inhibitor, suppresses growth and chemosensitizes leukemic cells through inhibition of gene expression regulated by TNF-TNFR1-TRADD-TRAF2-NIK-TAK1-IKK pathway” (published in 2011, cited 18 times):
This article has been retracted at the request of the Editor.
Fig. 4F, labeled Triptolide plus TNF in wild type mouse embryonic fibroblasts (Trp + TNF/MEF WT) was reused to represent TNF alone in knockout mouse embryonic fibroblasts (TNF/MEF p65−/−). The image has been manipulated in contrast, brightness and size to represent the different experimental conditions.
The article has been retracted because the data integrity has become questionable.
In addition to these new retractions, Aggarwal — who has seven papers each cited at least 1,000 times — has six corrections, two unexplained withdrawals, and two Expressions of Concern.
Update, 2/22/16, 4:11 p.m. Eastern: Aggarwal is no longer working at MD Anderson, according to a statement we just received from the institution:
Bharat B. Aggarwal retired from MD Anderson Cancer Center on December 31, 2015.
MD Anderson Cancer Center is committed to the highest standards of scientific integrity. Any scientific work that does not adhere to the highest standards of scientific integrity is not acceptable. MD Anderson also supports organizations and journals, like Biochemical Pharmacology, when questions of scientific integrity have been raised and they have determined that steps must be taken to correct the scientific record and ensure scientific integrity.
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Since 2012 we have been waiting for a conclusion from MD Anderson regarding their investigation of Aggarwal.
Will there be published any conclusions from MD Anderson or do they, as many other elite research institutions, prefer to sweep such problems under the carpet?
Openness in these cases is very important since there are a lot more articles that have been questioned at Pubpeer and in different science blogs, like this one:
http://md-anderson-cc.blogspot.no/
If you live in Texas, you can definitely request FOIA on Aggarwal. A recent U.S. Supreme Court decision allows states to FOIA to the citizen of a particular state.
Painful end of curcumin era at last. I remember that how many young researchers in my country were deeply influenced by his erroneous publications to work on curcumin. I was constantly mocked by my colleagues for not working with curcumin, but I never used it as I could never believe that a single compound can be a panacea for all diseases. And the final result is there for everyone to see and learn a lesson that excess of curcumin is equally bad for your health and career.
Certainly curcumin is not a cure-all, but surely pleiotropic molecules exist. There are tens of thousands of studies on curcumin (and other turmeric compounds) NOT involving Aggarwal that suggest a multitude of interesting and potentially beneficial properties.
MANY other studies involving curcumin (but not Aggarwal) were also faked. There was some guy at Wayne State University, one in Connecticut, one in Canada, one at George Washington University (if my memory is correct) whose papers on curcumin were subjects of misconduct charges and/or findings.
Certainly, there are many compounds and natural products that have beneficial properties, at least in some situations (how about penicillin, for example). But I will ALWAYS cringe when I read that there’s a compound that kills all cancer cells without harming normal cells. (I personally know people who worked with curcumin and claimed that, and I recently read that same claim made by a scientist regarding his work with a component of green tea.)
A case for going through his entire output? That would take time though. The continued citation of the retracted papers will doubtless provoke ironic laughter and hair tearing in equal measure.
One pattern that would be worth checking is the relationship between legal threats and eventual outcome of the investigations into the veracity of the data.
Scopus lists him with 630 papers. Going through his output would take some time then…
At last some movement on this case. Only 4 years and counting. Just to confirm, all 7 of these were reported by me to ORI in 2011, and posted on Juichii Jigen’s site (http://md-anderson-cc.blogspot.com/) around the same time.
What’s odd, is they appear to have missed one which I reported to ORI but wasn’t posted online. This suggests either they were not working from the ORI-provided (or institution-provided) list, or they knew about this example and just didn’t think it rose to the level necessary for action. Here it is anyway…
Biochem Pharmacol. 2005 Sep 1;70(5):700-13. Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. PMID 16023083.
Figure 3, b-actin loading control for curcumin time course in panel A and F is the same, despite claim in figure legend that blots from the proteins of interest in either panel were stripped and re-probed for b-actin. The individual blots have different band patterns (slope/spacing), so the claim regarding loading controls being from the same blots is demonstrably incorrect.
Let’s hope this spurs some other journals into action, in particular J. Immunol, who were sent a pack of 5 papers to deal with in 2012, and despite numerous emails and CC’ing COPE, have so far not bothered to even respond.
Many of the Aggarwal retractions do not outright dispute findings; could these be categorized as sloppy reporting and as such don’t rise to the level of questionable conclusions? Still, I am deeply troubled by the emergence of multiple studies questioning data integrity.
I do suspect that the sheer quantity of studies Aggarwal was included on suggests he may have actually been an undesignated corresponding author rather than a primary researcher in many of these…and should perhaps be a cautionary tale for ALL “corresponding” senior authors. Thoughts?
My interest in these studies, and retractions, as a plant scientist, lies with one of the key compounds, curcumin. Traditionally, curcumin is derived from Curcuma longa L. (turmeric). The source of curcumin that Aggarwal et al. indicate in their papers is from LKT Laboratories:
http://www.lktlabs.com/
Yet, the LKT Labs indicates two commercial sources:
C8069
http://www.lktlabs.com/products/Curcumin-58-0.html
C8070 (high purity)
http://www.lktlabs.com/products/Curcumin_high_purity-2422-0.html
I could not see the precise product used in these studies when I examined the papers. Perhaps the authors could indicate this very important detail, given the fact that this compound is being used for medical purposes.
I would also be interested to hear the opinion of resident commentators who are chemists or organic chemists, as to the effect of isolation technique, plant source (e.g., other Curcuma species) and other influencing factors that might influence the outcome of an experiment that uses “curcumin” (sensu lato). A Wiki page on curcumin:
https://en.wikipedia.org/wiki/Curcumin
What’s really frustrating about this whole thing is that Aggarwal is still able to get things published. Here’s a brand-new paper from this month (the 50th he’s published since initial problems were reported to ORI 4 years ago!) and it contains the same kind of potential image issues that anyone familiar with this case will recognize. In it, Aggarwal lists a gmail address for contact, consistent with departure from MD Anderson.
https://pubpeer.com/publications/26874195
http://imgur.com/jDbdX0l
That will make 16 retractions and a place on the leaderboard.
7 retractions JBC 5th August 2016.