The purpose of this study was to determine the effect of curcumin on Survivin/BIRC5 and on the role of signal transducer and activator of transcription 3 (STAT3) activation in Survivin/ BIRC5. We incubated two pancreatic cancer cell lines with different amounts of curcumin. This resulted in a downregulation of proliferation in all cell lines tested. The expression of Survivin/BIRC5 on mRNA and protein level was significantly downregulated and the phosphorylation of STAT3 was blocked. Treatment of pancreatic cancer cells with curcumin resulted in an induction of apoptosis. The results indicate that curcumin inhibits several key factors in cancer cellular pathways and may be of interest in pancreatic cancer.
"Recently, Georgiadou et al.  could demonstrate that vascular endothelial growth factor (VEGF) and Id-1 overexpression in PDAC were found to be associated with high microvessel density and was associated with a worse outcome in terms of patient survival. Additionally, curcumin has been shown to inhibit the growth of PDAC cell lines in vitro and in a mouse model by inhibiting various intracellular pathways including nuclear factor kappa B (NFkB), which is involved in angiogenesis  . Therefore, the potential of anti-angiogenic active VEGF directed multi tyrosine-kinase-inhibitors (TKI) such as the receptor TKI sunitinib should be assessed for improving the outcome in PDAC. "
"STA3 plays a role in the cancer development and progression and overexpression or high level of STAT3 has been observed in various types of cancers [134, 135]. Curcumin inhibits constitutive STAT3 phosphorylation . Other results also show that the curcumin significantly suppressed Stat3 phosphorylation in bronchoepithelial cells and lung cancer derived cells, indicative of Stat3 pathway suppression, and finally inhibits the proliferative capacity of bronchoepithelial cells and lung cancer cells . "
[Show abstract][Hide abstract] ABSTRACT: Cancer is the most dreadful disease worldwide in terms of morbidity and mortality. The exact cause of cancer development and progression is not fully known. But it is thought that cancer occurs due to the structural and functional changes in the genes. The current approach to cancer treatment based on allopathic is expensive, exhibits side effects; and may also alter the normal functioning of genes. Thus, a safe and effective mode of treatment is needed to control the cancer development and progression. Some medicinal plants provide a safe, effective and affordable remedy to control the progression of malignant cells. The importance of medicinal plants and their constituents has been documented in Ayurveda, Unani medicine, and various religious books. Curcumin, a vital constituent of the spice turmeric, is an alternative approach in the prevention of cancer. Earlier studies have shown the effect of curcumin as an antioxidant, antibacterial, antitumor and it also has a noteworthy role in the control of different diseases. In this review, we summarize the understanding of chemopreventive effects of curcumin in the prevention of cancer via the regulation of various cell signaling and genetic pathways.
BioMed Research International 09/2014; 2014:761608. DOI:10.1155/2014/761608 · 2.71 Impact Factor
"STAT3 is also known to protect cells from apoptosis through the upregulation of Bcl-xL, Bcl-2, and survivin. Elevated STAT3 activity has been detected in head and neck squamous cell carcinoma, leukemia, lymphoma and multiple myeloma , . In the current study, Mitocur-1 inhibited the STAT3 phosphorylation and downstream targets such as Bcl2 and Bax in MCF-cells. "
[Show abstract][Hide abstract] ABSTRACT: Although the anti-cancer effects of curcumin has been shown in various cancer cell types, in vitro, pre-clinical and clinical studies showed only a limited efficacy, even at high doses. This is presumably due to low bioavailability in both plasma and tissues, particularly due to poor intracellular accumulation. A variety of methods have been developed to achieve the selective targeting of drugs to cells and mitochondrion. We used a novel approach by conjugation of curcumin to lipophilic triphenylphosphonium (TPP) cation to facilitate delivery of curcumin to mitochondria. TPP is selectively taken up by mitochondria driven by the membrane potential by several hundred folds. In this study, three mitocurcuminoids (mitocurcuminoids-1, 2, and 3) were successfully synthesized by tagging TPP to curcumin at different positions. ESI-MS analysis showed significantly higher uptake of the mitocurcuminoids in mitochondria as compared to curcumin in MCF-7 breast cancer cells. All three mitocurcuminoids exhibited significant cytotoxicity to MCF-7, MDA-MB-231, SKNSH, DU-145, and HeLa cancer cells with minimal effect on normal mammary epithelial cells (MCF-10A). The IC50 was much lower for mitocurcuminoids when compared to curcumin. The mitocurcuminoids induced significant ROS generation, a drop in ΔØm, cell-cycle arrest and apoptosis. They inhibited Akt and STAT3 phosphorylation and increased ERK phosphorylation. Mitocurcuminoids also showed upregulation of pro-apoptotic BNIP3 expression. In conclusion, the results of this study indicated that mitocurcuminoids show substantial promise for further development as a potential agent for the treatment of various cancers.
PLoS ONE 03/2014; 9(3):e89351. DOI:10.1371/journal.pone.0089351 · 3.23 Impact Factor
K. Bougoffa-Sadaoui, E. Gontier, M.S. Telliez, M. Lequart-Pillon, H. Ouadid-Ahidouch, F. Maiza-Benabdesselam
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