RETRACTED: Curcumin potentiates the antitumor effects of gemcitabine in an orthotopic model of human bladder cancer through suppression of proliferative and angiogenic biomarkers
Authors: Bokyung Sung
Teruo Inamoto
Ashish M Kamat
Bharat B Aggarwal
Sheeja T Tharakan
Journal: Biochemical Pharmacology (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: bladder cancer; curcumin; gemcitabine; NF-kappaB; apoptosis
Affiliations: Department of Urology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, United States.

Abstract:  Little progress has been made in the last three decades in the treatment of bladder cancer. Novel agents that are nontoxic and can improve the current standard of care of this disease are urgently needed. Curcumin, a component of Curcuma longa (also called turmeric), is one such agent that has been shown to suppress pathways linked to oncogenesis, including cell survival, proliferation, invasion and angiogenesis. We investigated whether curcumin has potential to improve the current therapy for bladder cancer, using an orthotopic mouse model. Curcumin potentiated the apoptotic effects of gemcitabine against human bladder cancer 253JBV cells in culture. Electrophoretic mobility shift assay revealed that curcumin also suppressed the gemcitabine-induced activation of the cell survival transcription factor NF-kappaB. In an orthotopic mouse model, bioluminescence imaging revealed that while curcumin alone significantly reduced the bladder tumor volume, maximum reduction was observed when curcumin was used in combination with gemcitabine (P&lt;0.01 versus vehicle; P&lt;0.01 versus gemcitabine alone). Curcumin also significantly decreased the proliferation marker Ki-67 and microvessel density (CD31) (P&lt;0.01 versus vehicle; P&lt;0.01 versus gemcitabine alone), but maximum reduction occurred when it was combined with gemcitabine (P&lt;0.01 versus vehicle; P&lt;0.01 versus gemcitabine alone). Curcumin abolished the constitutive activation of NF-kappaB in the tumor tissue; induced apoptosis, and decreased cyclin D1, VEGF, COX-2, c-myc and Bcl-2 expression in the bladder cancer tissue. Overall our results suggest that curcumin alone exhibits significant antitumor effects against human bladder cancer and it further potentiates the effects of gemictabine, possibly through the modulation of NF-kappaB signaling pathway. 

Retracted: Yes

PubPeer comments:
 Readers should become aware of a recent preprint entitled  FRET-based Tau seeding assay does not represent prion-like templated assembly of Tau fibers , which argues that  that the interpretation of the FRET-effect is not tenable, because the TauRD-GFP in the sensor cells cannot assemble into PHF-like fibers upon adopting some misfolded Tau conformation transmitted from outside the cell. As such, this also invalidates the underlying assumption that only some extracellular misfolded tau could be the carrier of pathogenic information. From the abstract:  Using biophysical methods (light scattering, atomic force microscopy (AFM), and scanning-transmission electron microscopy (STEM)), we found that the assembly of TauRDu0394K-GFP was severely inhibited, even in the presence of nucleation enhancers (heparin and or pre-formed PHFs from TauRDu0394K). Some rare fiber-like particles had a very different subunit packing from proper PHFs, as judged by STEM. The mass per length (MPL) values of TauRDu0394K fibrils are equivalent to 4.45 molecules nm, close to the expected value for a paired-helical fiber with 2 protofilaments and cross-u03b2 structure. By contrast, the elongated particles formed by TauRDu0394K-GFP have MPL values around u223c2, less than half of the values expected for PHFs, indicating that the subunit packing is distinct. **Thus, both kinetic and structural observations are incompatible with a model whereby external Tau can form a template for PHF assembly of Tau-GFP in recipient cells. As a consequence, the observed local increase of FRET in recipient cells must be caused by other signalling processes** , 
 #1 Readers should become aware of rebuttals of Coloceras Grande s assertion by unbiased third parties and the original developers of the critiqued FRET-based tau seeding assays :  Kaniyappan et al. misrepresent the purpose of our cell-based FRET assay. The assay was engineered to detect exogenous pathological tau conformations, not to create endogenous PHFs. Within this framework, we and others have used this biosensor assay to detect pathologic tau aggregates in immunoprecipiated brain lysates from mice (Holmes et al. 2014) and humans (Furman et al. 2016), to track tau pathology through neuroanatomical circuits (Kaufman et al. 2018), to identify subcellular compartments that harbor tau aggregates (DeVos et al. 2018), to evaluate the efficacy of anti-tau therapeutics (Yanamandra et al. 2013; DeVos et al. 2017), and to characterize distinct seed-competent tau monomer (Mirbaha et al. 2018), including forms of monomer that encode distinct strains (Sharma et al. 2018). Additionally, aggregates that form in the FRET biosensor cells fluoresce in the presence of the amyloid-binding dye X-34, indicating a beta-sheet structure (Sanders et al. 2014). Further, tau immunodepletion of mouse and human brain lysates eliminates tau seeding in the FRET assay (Holmes et al. 2014), consistent with a model in which exogenous tau aggregates directly serve as templates for aggregation. Perhaps most importantly, similar cell-based assays detect and propagate unique tau conformational strains that have subsequently been propagated serially through a rodent model based on full-length (1N4R) human tau, and back into biosensors (Sanders et al. 2014). The simplest interpretation of this work is that tau-GFP fusions are faithfully propagating unique tau aggregate conformations. ,