Salicylates Inhibit NF-κB Activation and Enhance TNF-α-Induced Apoptosis in Human Pancreatic Cancer Cells

McDade, Theodore P.; Perugini, Richard A.; Vittimberga, Frank J.; Carrigan, Rebecca C.; Callery, Mark P.

doi:10.1006/jsre.1998.5560

Cited by 73 publications

(53 citation statements)

References 27 publications

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“…VP16 and doxorubicin. New strategies for combined chemotherapy of pancreatic tumors should be designed where speci®c blockade of NF-kB signi®cantly reduces the number of resistant cells (Jeremias et al, 1998;McDade et al, 1999;Wang et al, 1996), and thus the rate of relapses.…”

Section: Discussionmentioning

confidence: 99%

“…These tumors exhibit various alterations in their genetic repertoir of growth control and apoptosis, including the functional loss of p53 (Lam et al, 1999) and mutations in the topoIIa gene (Dingemans et al, 1999;Mao et al, 1999). Another mechanism by which tumor cells may have gained resistance to cytotoxic drugs includes the activation of NF-kB (Jeremias et al, 1998;McDade et al, 1999), a condition that has been recently reported for some pancreatic carcinoma cells (Wang et al, 1999a). Still, a close functional relation of the NF-kB status in pancreatic carcinoma cells and their resistance to chemotherapy remains to be investigated.…”

Section: Introductionmentioning

confidence: 97%

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Inhibition of NF-κB sensitizes human pancreatic carcinoma cells to apoptosis induced by etoposide (VP16) or doxorubicin

et al. 2001

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The transcription factor NF-kB has anti-apoptotic properties and may confer chemoresistance to cancer cells. Here, we describe human pancreatic carcinoma cell lines that di er in the responsiveness to the topoisomerase-2 inhibitors VP16 (20 mM) and doxorubicin (0.3 mM): Highly sensitive BxPC-3 and PT45-P1 cells, and Capan-1 and A818-4 cells that were almost resistant to both anti cancer drugs. VP16, but not doxorubicin, transiently induced NF-kB activity in all cell lines, whereas basal NF-kB binding was nearly undetectable in BxPc-3 and PT45-P1 cells, but rather high in Capan-1 and A818-4 cells, as demonstrated by gel-shift and luciferase assays. Treatment with various NF-kB inhibitors (Gliotoxin, MG132 and Sulfasalazine), or transfection with the IkBa super-repressor, strongly enhanced the apoptotic e ects of VP16 or doxorubicin on resistant Capan-1 and 818-4 cells. Our results indicate that under certain conditions the resistance of pancreatic carcinoma cells to chemotherapy is due to their constitutive NF-kB activity rather than the transient induction of NF-kB by some anti-cancer drugs. Blockade of basal NF-kB activity by well established drugs e ciently reduces chemoresistance of pancreatic cancer cells and o ers the potential for improved therapeutic strategies. Oncogene (2001) 20, 859 ± 868.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Inhibition of NF-κB sensitizes human pancreatic carcinoma cells to apoptosis induced by etoposide (VP16) or doxorubicin

et al. 2001

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“…Previously, NF-B has been observed in normal endometrium, where its actions seem to be under the control of ovarian steroids. 25 Progesterone is able to repress the transcriptional activity of NF-B, 51 and, during the perimenstrual phase, which is associated with a decrease in serum progesterone concentrations, mRNA synthesis and the transcriptional activity of NF-B are increased. 25 In malignancies, NF-B has been observed to be associated with increased expression of matrix metallo-proteinases, which can promote invasiveness and metastasis formation of malignant cells 52 and induce neovascularization.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis and apoptosis‐related factors Bcl‐2, Bax, tumor necrosis factor‐α, and NF‐κB in human endometrial hyperplasia and carcinoma

Vaskivuo

Stenbäck

Tapanainen

2002

Cancer

112

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BACKGROUNDApoptosis controls cell homeostasis in the endometrium during normal menstrual cycles, and morphologic studies have suggested its association with the development of endometrial carcinoma. Apoptosis is regulated by several genes, especially those of the Bcl‐2 gene family, but their significance in endometrial pathologies is not well understood.METHODSTo study the role and regulation of apoptosis in endometrial hyperplasia and carcinoma, human endometrial specimens were analyzed using in situ 3′‐end labeling of apoptotic cells and in situ hybridization and immunohistochemistry of apoptosis‐related factors.RESULTSApoptosis was scarce in normal proliferating endometrium as well as in simplex, complex, and atypical hyperplasia and was low in Grade I adenocarcinoma. In Grade II adenocarcinoma a significant increase in the rate of apoptosis was observed. Apoptosis decreased in Grade III adenocarcinoma, but it was still higher than in normal or hyperplastic endometrium. Bcl‐2 and Bax were expressed in normal and hyperplastic endometrium, and the Bcl‐2/Bax ratio was lower in endometrial carcinoma. Tumor necrosis factor‐α was expressed in normal endometrium and simplex and complex hyperplasia, but it was down‐regulated in atypical hyperplasia and endometrial carcinoma. The transcription factor NF‐κB was present in proliferating endometrium and in endometrial hyperplasia, but its expression was lower in carcinoma.CONCLUSIONSIn endometrial proliferation and hyperplasia a low rate of apoptosis is present. In Grade I carcinoma the rate of apoptosis is decreased, but the rate is subsequently increased in advanced carcinoma. The decrease in the rate of apoptosis in Grade III adenocarcinoma may reflect loss of control of cell homeostasis, decreased differentiation, and increased malignancy. Cancer 2002;95:1463–71. © 2002 American Cancer Society.DOI 10.1002/cncr.10876

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“…These include tumor cell lines of lymphoid origin, such as T-cell lymphoma Hut 78 cells (Giri et al, 1998), multiple myeloma (Feinman et al, 1999) and Hodgkin/ Reed Sternberg cells (Bargou et al, 1996(Bargou et al, , 1997Krappmann et al, 1999). In addition, non-lymphoid cell lines exhibit enhanced NF-kB activity, including breast cancer cells (Nakshatri et al, 1997;Sovak et al, 1997), ovarian cancer cells (Bours et al, 1994), bladder cancer cells (Sumitomo et al, 1999), melanomas (Shattuck-Brandt and Richmond, 1997), lung carcinoma (Batra et al, 1999;Mukhopadhyay et al, 1995), thyroid carcinoma (Visconti et al, 1997), pancreatic cancer cells (McDade et al, 1999;Wang et al, 1999c), head and neck squamous cell carcinomas and ovarian carcinoma cell lines (Bours et al, 1994).…”

Section: Bcl-2mentioning

confidence: 99%

Control of apoptosis by Rel/NF-κB transcription factors

1999

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Salicylates Inhibit NF-κB Activation and Enhance TNF-α-Induced Apoptosis in Human Pancreatic Cancer Cells

Cited by 73 publications

References 27 publications

Inhibition of NF-κB sensitizes human pancreatic carcinoma cells to apoptosis induced by etoposide (VP16) or doxorubicin

Inhibition of NF-κB sensitizes human pancreatic carcinoma cells to apoptosis induced by etoposide (VP16) or doxorubicin

Apoptosis and apoptosis‐related factors Bcl‐2, Bax, tumor necrosis factor‐α, and NF‐κB in human endometrial hyperplasia and carcinoma

Control of apoptosis by Rel/NF-κB transcription factors

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