Therapeutic Potential of “Rexinoids” in Cancer Prevention and Treatment

Tanaka, Takemi; Luca, Luigi M. De

doi:10.1158/0008-5472.can-08-4407

Cited by 66 publications

(62 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, marked deregulation of ribosomal-and translation-related genes in patients with the 5q-syndrome has been shown by our group. 62 Multiple pathways that have an important function in cell survival, differentiation, apoptosis and growth [63][64][65][66] were significantly deregulated in À7/del(7q) MDS, including SAPK/JNK, NF-kB, PI3K/AKT and ceramide signaling pathways. Interestingly, CK2, an enzyme with a master regulatory function in Wnt and NF-kB signaling, is up-regulated in À7/del(7q) MDS by 4twofold.…”

Section: Deregulated Pathways In Myelodysplastic Syndromes a Pellagatmentioning

confidence: 99%

Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells

et al. 2010

View full text Add to dashboard Cite

To gain insight into the molecular pathogenesis of the myelodysplastic syndromes (MDS), we performed global gene expression profiling and pathway analysis on the hematopoietic stem cells (HSC) of 183 MDS patients as compared with the HSC of 17 healthy controls. The most significantly deregulated pathways in MDS include interferon signaling, thrombopoietin signaling and the Wnt pathways. Among the most significantly deregulated gene pathways in early MDS are immunodeficiency, apoptosis and chemokine signaling, whereas advanced MDS is characterized by deregulation of DNA damage response and checkpoint pathways. We have identified distinct gene expression profiles and deregulated gene pathways in patients with del(5q), trisomy 8 or À7/del(7q). Patients with trisomy 8 are characterized by deregulation of pathways involved in the immune response, patients with À7/del(7q) by pathways involved in cell survival, whereas patients with del(5q) show deregulation of integrin signaling and cell cycle regulation pathways. This is the first study to determine deregulated gene pathways and ontology groups in the HSC of a large group of MDS patients. The deregulated pathways identified are likely to be critical to the MDS HSC phenotype and give new insights into the molecular pathogenesis of this disorder, thereby providing new targets for therapeutic intervention.

show abstract

Section: Deregulated Pathways In Myelodysplastic Syndromes a Pellagatmentioning

confidence: 99%

Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells

et al. 2010

View full text Add to dashboard Cite

show abstract

“…In accordance with the third hypothesis stating that the transretinoic acids in the saffron has an anti-tumour activity we have identified Retinoic acid receptor alpha as a potential receptor. Retinoid-dependent activation of RARα arrests the growth, while activation of the other receptor favours the proliferation of the neoplastic cell (Tanaka and De Luca, 2009;Tang et al, 2011). This result also very well correlates with the experimental evidences.…”

Section: Potential Protein Targets For Crocetinmentioning

confidence: 99%

Comparative Reverse Screening Approach to Identify Potential Anti-neoplastic Targets of Saffron Functional Components and Binding Mode

Bhattacharjee¹,

Vijayasarathy²,

Karunakar³

et al. 2012

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: In the last two decades, pioneering research on anti-tumour activity of saffron has shed light on the role of crocetin, picrocrocin and safranal, as broad spectrum anti-neoplastic agents. However, the exact mechanisms have yet to be elucidated. Identification and characterization of the targets of bioactive constituents will play an imperative role in demystifying the complex anti-neoplastic machinery. Methods: In the quest of potential target identification, a dual virtual screening approach utilizing two inverse screening systems, one predicated on idTarget and the other on PharmMapper was here employed. A set of target proteins associated with multiple forms of cancer and ranked by Fit Score and Binding energy were obtained from the two independent inverse screening platforms. The validity of the results was checked by meticulously analyzing the post-docking binding pose of the picrocrocin with Hsp90 alpha in AutoDock. Results: The docking pose reveals that electrostatic and hydrogen bonds play the key role in inter-molecular interactions in ligand binding. Picrocrocin binds to the Hsp90 alpha with a definite orientation appropriate for nucleophilic attacks by several electrical residues inside the Hsp90-alpha ATPase catalytic site. Conclusion: This study reveals functional information about the anti-tumor mechanism of saffron bioactive constituents. Also, a tractable set of anti-neoplastic targets for saffron has been generated in this study which can be further authenticated by in vivo and in vitro experiments.

show abstract

“…It is a very unique protein with the ability to form heterodimers with one third of the 48 other nuclear receptors giving it the potential to converge a large array of signaling pathways. The RXR can form homodimers, permissive heterodimers, and non-permissive heterodimers in a ligand-dependent or -independent manner (Tanaka and De Luca, 2009). When RXR forms homodimers or permissive heterodimers (with PPAR, LXR, PXR etc.…”

Section: The Retinoid X and Retinoic Acid Receptorsmentioning

confidence: 99%

“…When RXR forms non-permissive heterodimers (with RAR, VDR, TR etc. ), it is not activated by ligand, as the binding of the partner receptor to RXR allosterically inhibits it (Kurokawa et al, 1994;Tanaka et al, 2009). Furthermore, the activation domain of the partner is not located in proximity to ligand activated residues in the RXR interface (Bourguet et al, 2000;Gampe, Jr. et al, 2000b).…”

Section: The Retinoid X and Retinoic Acid Receptorsmentioning

confidence: 99%