Search

Your search keyword '"Ali, Shadan"' showing total 31 results
Start Over Author "Ali, Shadan" Journal cancer research
31 results on '"Ali, Shadan"'

24. Acquisition of Epithelial-Mesenchymal Transition Phenotype of Gemcitabine-Resistant Pancreatic Cancer Cells Is Linked with Activation of the Notch Signaling Pathway

Author

Wang, Zhiwei, primary, Li, Yiwei, additional, Kong, Dejuan, additional, Banerjee, Sanjeev, additional, Ahmad, Aamir, additional, Azmi, Asfar Sohail, additional, Ali, Shadan, additional, Abbruzzese, James L., additional, Gallick, Gary E., additional, and Sarkar, Fazlul H., additional

Published
2009
Full Text
View/download PDF

29. Up-regulation of miR-146a contributes to the inhibition of invasion of pancreatic cancer cells.

Author

Li Y, VandenBoom TG 2nd, Wang Z, Kong D, Ali S, Philip PA, and Sarkar FH

Abstract

Pancreatic cancer (PC) is an aggressive malignancy with high mortality and is believed to be in part due to its highly invasive and metastatic behavior, which is associated with over-expression of EGFR and activation of NF-κB. Emerging evidence also suggest critical roles of microRNAs (miRNAs) in the regulation of various pathobiological processes including metastasis in PC and in other human malignancies. In the present study, we found lower expression of miR-146a in PC cells compared to normal human pancreatic duct epithelial (HPDE) cells. Interestingly, re-expression of miR-146a inhibited the invasive capacity of Colo357 and Panc-1 PC cells with concomitant down-regulation of EGFR and IRAK-1. Mechanistic studies including miR-146a re-expression, anti-miR-146 transfection, and EGFR knock-down experiment showed that there was a crosstalk between EGFR, MTA-2, IRAK-1, IκBα and NF-κB. Most importantly, we found that the treatment of PC cells with "natural agents" [3,3'-diinodolylmethane (DIM) or isoflavone] led to an increase in the expression of miR-146a and consequently down-regulated the expression of EGFR, MTA-2, IRAK-1 and NF-κB, resulting in the inhibition of invasion of Colo357 and Panc-1 cells. These results provide experimental evidence in support of the role of DIM and isoflavone as potential non-toxic agents as regulators of miRNA, which could be useful for the inhibition of cancer cell invasion and metastasis, and further suggesting that these agents could be important for designing novel targeted strategy for the treatment of PC.

Published
2010
Full Text
View/download PDF

30. Potentiation of the effect of erlotinib by genistein in pancreatic cancer: the role of Akt and nuclear factor-kappaB.

Author

El-Rayes BF, Ali S, Ali IF, Philip PA, Abbruzzese J, and Sarkar FH

Subjects
Apoptosis drug effects, Cell Line, Tumor, Cell Survival drug effects, Deoxycytidine analogs & derivatives, Deoxycytidine pharmacology, Drug Synergism, ErbB Receptors physiology, Erlotinib Hydrochloride, Humans, Phosphorylation, Signal Transduction drug effects, Gemcitabine, Genistein pharmacology, NF-kappa B physiology, Pancreatic Neoplasms drug therapy, Proto-Oncogene Proteins c-akt physiology, Quinazolines pharmacology
Abstract

The epidermal growth factor receptor (EGFR) is a target of new therapies in most nonhematologic cancers. EGFR blockade alone may not be sufficient for the control of growth and invasion of human pancreas cancer because of the independent activation of Akt and nuclear factor-kappaB (NF-kappaB). The expression of EGFR, Akt, and NF-kappaB was determined in six human pancreatic cancer cell lines. Selected cells for specific expression were treated with erlotinib, genistein, gemcitabine, or the combination. Growth inhibition was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and apoptosis was assayed by ELISA. EGFR, phosphorylated EGFR, phosphorylated Akt, and survivin expressions were determined by immunoblotting. Electrophoretic mobility shift assay was used to evaluate the DNA binding activity of NF-kappaB. Genistein significantly increased (P < 0.05) erlotinib-induced growth inhibition and apoptosis in BxPC-3, CAPAN-2, and AsPC-1 cells. In the BxPC-3 cell line, significant down-regulation of EGFR, phosphorylated Akt, NF-kappaB activation, and survivin was observed in the cells treated with the combination compared with the erlotinib-treated cells. In the HPAC and MIAPaCa cell line, no potentiation of the effects of erlotinib by genistein on cell growth or inhibition of the EGFR/Akt/NF-kappaB was observed. Genistein potentiated growth inhibition and apoptosis of the gemcitabine and erlotinib combination in COLO-357 cell line. Genistein potentiates the growth inhibition and apoptosis induced by erlotinib and gemcitabine in certain pancreatic cancer cells. Akt and NF-kappaB inhibition represents one of the mechanisms for the potentiation of erlotinib- and gemcitabine-induced cell death by genistein.

Published
2006
Full Text
View/download PDF

31. Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells.

Author

Li Y, Ahmed F, Ali S, Philip PA, Kucuk O, and Sarkar FH

Subjects
Breast Neoplasms drug therapy, Breast Neoplasms pathology, Cell Growth Processes drug effects, Cell Line, Tumor, Cisplatin administration & dosage, Cisplatin pharmacology, Docetaxel, Doxorubicin administration & dosage, Doxorubicin pharmacology, Drug Synergism, Genistein administration & dosage, Humans, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Male, Neoplasms pathology, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology, Prostatic Neoplasms drug therapy, Prostatic Neoplasms pathology, Taxoids administration & dosage, Taxoids pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Apoptosis drug effects, Genistein pharmacology, NF-kappa B antagonists & inhibitors, Neoplasms drug therapy
Abstract

Cancer chemotherapeutic strategies commonly require multiple agents. However, use of multiple agents contributes to added toxicity resulting in poor treatment outcome. Thus, combination chemotherapy must be optimized to increase tumor response and at the same time lower its toxicity. Chemotherapeutic agents are known to induce nuclear factor kappaB (NF-kappaB) activity in tumor cells, resulting in lower cell killing and drug resistance. In contrast, genistein has been shown to inhibit the activity of NF-kappaB and the growth of various cancer cells without causing systemic toxicity. We therefore investigated whether the inactivation of NF-kappaB by genistein before treatment of various cancer cells with chemotherapeutic agents could lead to better tumor cell killing as tested by in vitro studies using gene transfections and also by animal studies. PC-3 (prostate), MDA-MB-231 (breast), H460 (lung), and BxPC-3 (pancreas) cancer cells were pretreated with 15 to 30 micromol/L genistein for 24 hours and then exposed to low doses of chemotherapeutic agents for an additional 48 to 72 hours. We found that 15 to 30 micromol/L genistein combined with 100 to 500 nmol/L cisplatin, 0.5 to 2 nmol/L docetaxel, or 50 ng/mL doxorubicin resulted in significantly greater inhibition of cell growth and induction of apoptosis compared with either agent alone. Moreover, we found that the NF-kappaB activity was significantly increased within 2 hours of cisplatin and docetaxel treatment and that the NF-kappaB inducing activity of these agents was completely abrogated in cells pretreated with genistein. These results were also supported, for the first time, by animal experiments, p65 cDNA transfection and p65 small interfering RNA studies, which clearly showed that a specific target (NF-kappaB) was affected in vivo. Collectively, our results clearly suggest that genistein pretreatment inactivates NF-kappaB and may contribute to increased growth inhibition and apoptosis induced by cisplatin, docetaxel, and doxorubicin in prostate, breast, lung, and pancreatic cancer cells. Theses results warrant carefully designed clinical studies investigating the combination of soy isoflavones and commonly used chemotherapeutic agents for the treatment of human cancers.

Published
2005
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results