scholarly journals 1,1-Bis(3'-indolyl)-1-(p-bromophenyl)methane and related compounds repress survivin and decrease γ-radiation-induced survivin in colon and pancreatic cancer cells

2009 ◽  
Vol 35 (05) ◽  
Author(s):  
Safe
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Γ Radiation ◽  
Pancreatic Cancer Cells ◽  
Radiation Induced ◽  
Related Compounds

Effect of inhibition of poly-(ADP ribose) polymerase on gemcitabine and radiation-induced cytotoxicity of pancreatic cancer cells.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 203-203
Author(s):  
R. Tuli ◽  
A. Surmak ◽  
A. Blackford ◽  
A. Leubner ◽  
E. M. Jaffee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Death ◽  
Dna Repair ◽  
Cancer Cells ◽  
Parp Inhibitor ◽  
Parp Inhibition ◽  
Pancreatic Cancer Cells ◽  
Synergistic Mechanism ◽  
Radiation Induced ◽  
Parp 1

203 Background: Poly-(ADP ribose) polymerases (PARPs) are DNA-binding proteins involved in DNA repair. PARP inhibition has resulted in excellent antitumor activity when used with other cytotoxic therapies. ABT-888 is a promising PARP inhibitor with excellent potency against the PARP-1/2 enzymes and good oral bioavailability. We attempt to determine whether PARP-1/2 inhibition alone, or in combination with gemcitabine, will enhance the effects of irradiation (RT) of pancreatic cancer cells. Methods: The pancreatic carcinoma cell lines, MiaPaCa-2 and Panc02, were treated with ABT-888, gemcitabine, RT, or combinations thereof. RT was delivered with a 137-Cs Gammacell in a single fraction. Cells were pre-treated once with ABT-888 and/or gemcitabine 30 minutes prior to RT. Viability was assessed through reduction of resazurin into fluorescent resorufin. Levels of apoptosis were determined by measuring caspase-3/7 activity using a luminescent assay. PARP activity was determined using a chemiluminescent PAR elisa. Results: The half maximal inhibitory concentration (IC50) of RT was 5 Gy; IC10 for ABT-888 and gemcitabine were 10 uM and 5 nM, respectively. Treatment with ABT-888 (10 uM), gemcitabine (5 nM), or combinations of the two with RT led to increasingly higher rates of cell death 8 days after treatment (p<0.001). RT dose enhancement factors were 1.5, 1.82 and 2.36 for 1, 10 and 100 uM ABT-888, respectively. Minimal cytotoxicity was noted when cells were treated with ABT-888 alone up to 100 uM. Caspase activity was not significantly increased when treated with ABT-888 (10 uM) alone (1.28 fold, p=0.077), but became significant when RT (2 Gy) was added (2.03 fold, p=0.006). This difference was further enhanced by the addition of gemcitabine (2.95 fold, p=0.004). Conclusions: ABT-888 is a potent radiosensitizer of pancreatic cancer cells with minimal cytotoxicity when used alone. Cell death is further potentiated by cotreatment with gemcitabine. Radiation-induced apoptosis was significantly enhanced by ABT-888 and gemcitabine, suggesting a synergistic mechanism of interference with DNA repair. These data are currently being validated in an orthotopic pancreatic cancer mouse model. No significant financial relationships to disclose.

Ascorbate Augments Radiation-induced DNA Damage and Cytotoxicity in Pancreatic Cancer Cells

2010 ◽  
Vol 49 ◽  
pp. S58-S59
Author(s):  
Juan Du ◽  
Amanda Kalen ◽  
Zita Sibenaller ◽  
Prabhat Goswami ◽  
Joseph Cullen
Keyword(s):  
Pancreatic Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Pancreatic Cancer Cells ◽  
Radiation Induced

Tumor treating fields (TTF) treatment enhances radiation-induced apoptosis in pancreatic cancer cells

2020 ◽  
Vol 96 (12) ◽  
pp. 1528-1533
Author(s):  
Yunhui Jo ◽  
Geon Oh ◽  
Yongha Gi ◽  
Heehun Sung ◽  
Eun Bin Joo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Tumor Treating Fields ◽  
Pancreatic Cancer Cells ◽  
Radiation Induced ◽  
Induced Apoptosis

scholarly journals Inhibition of Radiation-Induced DNA Repair and Prosurvival Pathways Contributes to Vorinostat-Mediated Radiosensitization of Pancreatic Cancer Cells

Pancreas ◽  
2010 ◽  
Vol 39 (8) ◽  
pp. 1277-1283 ◽  
Author(s):  
Amit Deorukhkar ◽  
Shujun Shentu ◽  
Hee Chul Park ◽  
Parmeswaran Diagaradjane ◽  
Vinay Puduvalli ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dna Repair ◽  
Cancer Cells ◽  
Pancreatic Cancer Cells ◽  
Radiation Induced

scholarly journals Catalase Modulates the Radio-Sensitization of Pancreatic Cancer Cells by Pharmacological Ascorbate

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 614
Author(s):  
Juan Du ◽  
Rory S. Carroll ◽  
Garett J. Steers ◽  
Brett A. Wagner ◽  
Brianne R. O’Leary ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Standard Of Care ◽  
Related Factor ◽  
Dual Roles ◽  
Normal Cells ◽  
Pancreatic Cancer Cells ◽  
Radiation Induced ◽  
Long Term Survivors

Pancreatic cancer cells (PDACs) are more susceptible to an oxidative insult than normal cells, resulting in greater cytotoxicity upon exposure to agents that increase pro-oxidant levels. Pharmacological ascorbate (P-AscH−), i.e., large amounts given intravenously (IV), generates significant fluxes of hydrogen peroxide (H2O2), resulting in the killing of PDACs but not normal cells. Recent studies have demonstrated that P-AscH− radio-sensitizes PDAC but is a radioprotector to normal cells and tissues. Several mechanisms have been hypothesized to explain the dual roles of P-AscH− in radiation-induced toxicity including the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2), RelB, as well as changes in bioenergetic profiles. We have found that P-AscH− in conjunction with radiation increases Nrf2 in both cancer cells and normal cells. Although P-AscH− with radiation decreases RelB in cancer cells vs. normal cells, the knockout of RelB does not radio-sensitize PDACs. Cellular bioenergetic profiles demonstrate that P-AscH− with radiation increases the ATP demand/production rate (glycolytic and oxidative phosphorylation) in both PDACs and normal cells. Knocking out catalase results in P-AscH− radio-sensitization in PDACs. In a phase I trial where P-AscH− was included as an adjuvant to the standard of care, short-term survivors had higher catalase levels in tumor tissue, compared to long-term survivors. These data suggest that P-AscH− radio-sensitizes PDACs through increased peroxide flux. Catalase levels could be a possible indicator for how tumors will respond to P-AscH−.

scholarly journals Role of α5β1 Integrin Up-regulation in Radiation-Induced Invasion by Human Pancreatic Cancer Cells

2011 ◽  
Vol 4 (5) ◽  
pp. 282-292 ◽  
Author(s):  
Hongren Yao ◽  
Zhao-Zhu Zeng ◽  
Kevin S. Fay ◽  
Donna M. Veine ◽  
Evan D. Staszewski ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Radiation Induced ◽  
Α5β1 Integrin

scholarly journals The CD44 standard isoform contributes to radioresistance of pancreatic cancer cells

2017 ◽  
Vol 58 (6) ◽  
pp. 816-826 ◽  
Author(s):  
Kento Tsubouchi ◽  
Kazumasa Minami ◽  
Naoki Hayashi ◽  
Yuhki Yokoyama ◽  
Seiji Mori ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Stem Cell Marker ◽  
Human Pancreatic Cancer ◽  
X Rays ◽  
Cd44 Isoforms ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells ◽  
Radiation Induced

Abstract Resistance to chemoradiotherapy is one reason for the increased recurrence rate of pancreatic cancer after these therapies. These cells change the expression levels of several proteins, such as epithelial–mesenchymal transition (EMT), while acquiring the chemo- or radio-resistance. In this study, we focused on CD44, a pancreatic cancer stem cell marker. CD44 has isoforms with different functions: standard isoform (CD44s) and several variant isoforms (CD44v). However, little is known about the roles of these isoforms after ionizing irradiation. The purpose of this study was to investigate the role of CD44 isoforms in radioresistance of pancreatic cancer cells. AsPC-1 (a human pancreatic cancer cell line) was irradiated with 4 MV X-rays. The mRNA and protein levels of CD44s were strongly upregulated, dose dependently, compared with CD44v after irradiation. Thus, we further investigated CD44s at the point of cell proliferation. We evaluated cell proliferation and survival, using CD44s knockdown cells. CD44s knockdown did not change the proliferation rate for up to 72 h after the irradiation, but decreased cell viability in the colony formation assay. As one of the reasons for these effects, we found downregulation of phosphorylated extracellular signal–regulated kinase (Erk; which is involved with cell proliferation) by CD44s knockdown, time dependently. Moreover, radiation-induced EMT-like expression changes were detected and suppressed by CD44s knockdown. In conclusion, our work demonstrated that CD44 standard isoform was especially upregulated after high-dose X-ray irradiation in several isoforms of CD44 and contributed to longer-term cell survival after the irradiation through the maintenance of Erk phosphorylation and radiation-induced EMT.

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