Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF.
Shadan Ali,Aamir Ahmad,Sanjeev Banerjee,Subhash Padhye,Kristin Dominiak,Jacqueline M. Schaffert,Zhiwei Wang,Philip A. Philip,Fazlul H. Sarkar +8 more
TLDR
A significant reduction in cell viability was revealed in CDF-treated cells compared with curcumin- treated cells, which were also associated with the induction of apoptosis, and these results were consistent with the downregulation of Akt, cyclooxygenase-2, prostaglandin E(2), vascular endothelial growth factor, and NF-kappaB DNA binding activity.Abstract:
Curcumin induces cancer cell growth arrest and apoptosis in vitro , but its poor bioavailability in vivo limits its antitumor efficacy. We have previously evaluated the bioavailability of novel analogues of curcumin compared with curcumin, and we found that the analogue CDF exhibited greater systemic and pancreatic tissue bioavailability. In this study, we evaluated the effects of CDF or curcumin alone or in combination with gemcitabine on cell viability and apoptosis in gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer (PC) cell lines. Mechanistic investigations revealed a significant reduction in cell viability in CDF-treated cells compared with curcumin-treated cells, which were also associated with the induction of apoptosis, and these results were consistent with the downregulation of Akt, cyclooxygenase-2, prostaglandin E 2 , vascular endothelial growth factor, and NF-κB DNA binding activity. We have also documented attenuated expression of miR-200 and increased expression of miR-21 (a signature of tumor aggressiveness) in gemcitabine-resistant cells relative to gemcitabine-sensitive cells. Interestingly, CDF treatment upregulated miR-200 expression and downregulated the expression of miR-21, and the downregulation of miR-21 resulted in the induction of PTEN. These results prompt further interest in CDF as a drug modality to improve treatment outcome of patients diagnosed with PC as a result of its greater bioavailability in pancreatic tissue. Cancer Res; 70(9); 3606–17. ©2010 AACR.read more
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Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression
Limo Chen,Don L. Gibbons,Sangeeta Goswami,Maria Angelica Cortez,Young Ho Ahn,Lauren Averett Byers,Xuejun Zhang,Xiaohui Yi,David Dwyer,Wei Lin,Lixia Diao,Jing Wang,Jonathon D. Roybal,Mayuri Patel,Christin Ungewiss,David H. Peng,Scott J. Antonia,Melanie Mediavilla-Varela,Gordon Robertson,Steve Jones,Milind Suraokar,James W. Welsh,Baruch Erez,Ignacio I. Wistuba,Lieping Chen,Di Peng,Shanshan Wang,Stephen E. Ullrich,John V. Heymach,Jonathan M. Kurie,F. Xiao Feng Qin,F. Xiao Feng Qin +31 more
TL;DR: A molecular link between epithelial-to-mesenchymal transition (EMT) and CD8+ TIL immunosuppression and cancer progression is demonstrated and ZEB1 promotes metastasis through a heretofore unappreciated cell non-autonomous mechanism, and subgroups of patients in whom malignant progression is driven by EMT activators may respond to treatment with PD-L1 antagonists.
Journal ArticleDOI
Bortezomib as the First Proteasome Inhibitor Anticancer Drug: Current Status and Future Perspectives
TL;DR: Findings could help guide physicians in refining the clinical use of bortezomib, and encourage basic scientists to generate next generation proteasome inhibitors that broaden the spectrum of efficacy and produce a more durable clinical response in cancer patients.
Journal ArticleDOI
One-step, multiplexed fluorescence detection of microRNAs based on duplex-specific nuclease signal amplification.
TL;DR: The duplex-specific nuclease is employed to recycle the process of target-assisted digestion of Taqman probes, resulting in a significant fluorescence signal amplification through which one target molecule cleaves thousands of probe molecules, and the efficiency of this DSNSA strategy for rapid direct quantification of multiple miRNAs in biological samples is demonstrated.
Journal ArticleDOI
Cancer chemoprevention by dietary polyphenols: promising role for epigenetics.
TL;DR: It is emphasized how increased understanding of the chemopreventive effects of dietary polyphenols on specific epigenetic alterations may provide unique and yet unexplored novel and highly effective chemopresventive strategies for reducing the health burden of cancer and other diseases in humans.
Journal ArticleDOI
The Molecular Basis for the Pharmacokinetics and Pharmacodynamics of Curcumin and Its Metabolites in Relation to Cancer
TL;DR: This review addresses the oncopharmacological properties of curcumin at the molecular level, whereby the phenotypical/biological changes induced in cancer cells upon completion of theCurcumin-triggered signaling cascade(s) are addressed in the framework of the hallmarks of cancer.
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