Curcumin mediated down-regulation of αV β3 integrin and up-regulation of pyruvate dehydrogenase kinase 4 (PDK4) in Erlotinib resistant SW480 colon cancer cells

2017 ◽  
Vol 32 (2) ◽  
pp. 355-364 ◽  
Author(s):  
Samira Javadi ◽  
Kobra Rostamizadeh ◽  
Jalal Hejazi ◽  
Maliheh Parsa ◽  
Mojtaba Fathi
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Kinase ◽  
Colon Cancer Cells ◽  
Down Regulation ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
Β3 Integrin

scholarly journals Transforming Growth Factor β Mediates Drug Resistance by Regulating the Expression of Pyruvate Dehydrogenase Kinase 4 in Colorectal Cancer

2016 ◽  
Vol 291 (33) ◽  
pp. 17405-17416 ◽  
Author(s):  
Yang Zhang ◽  
Yi Zhang ◽  
Liying Geng ◽  
Haowei Yi ◽  
Wei Huo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Kinase ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
Mouse Xenograft Model

Drug resistance is one of the main causes of colon cancer recurrence. However, our understanding of the underlying mechanisms and availability of therapeutic options remains limited. Here we show that expression of pyruvate dehydrogenase kinase 4 (PDK4) is positively correlated with drug resistance of colon cancer cells and induced by 5-fluorouracil (5-FU) treatment in drug-resistant but not drug-sensitive cells. Knockdown of PDK4 expression sensitizes colon cancer cells to 5-FU or oxaliplatin-induced apoptosis in vitro and increases the effectiveness of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. In addition, we demonstrate for the first time that TGFβ mediates drug resistance by regulating PDK4 expression and that 5-FU induces PDK4 expression in a TGFβ signaling-dependent manner. Mechanistically, knockdown or inhibition of PDK4 significantly increases the inhibitory effect of 5-FU on expression of the anti-apoptotic factors Bcl-2 and survivin. Importantly, studies of patient samples indicate that expression of PDK4 and phosphorylation of Smad2, an indicator of TGFβ pathway activation, show a strong correlation and that both positively associate with chemoresistance in colorectal cancer. These findings indicate that the TGFβ/PDK4 signaling axis plays an important role in the response of colorectal cancer to chemotherapy. A major implication of our studies is that inhibition of PDK4 may have considerable therapeutic potential to overcome drug resistance in colorectal cancer patients, which warrants the development of PDK4-specific inhibitors.

scholarly journals Cytotoxic Activity of Rearranged Drimane Meroterpenoids against Colon Cancer Cells via Down-Regulation of β-Catenin Expression

2015 ◽  
Vol 78 (3) ◽  
pp. 453-461 ◽  
Author(s):  
In Hyun Hwang ◽  
Joonseok Oh ◽  
Wei Zhou ◽  
Seoyoung Park ◽  
Joo-Hyun Kim ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
Down Regulation

Down-regulation of thymidylate synthase expression and its steady-state mRNA by oxaliplatin in colon cancer cells

2004 ◽  
Vol 15 (4) ◽  
pp. 371-376 ◽  
Author(s):  
Kun-Huei Yeh ◽  
Ann-Lii Cheng ◽  
Joeu-Pei Wan ◽  
Chien-Shing Lin ◽  
Chih-Chun Liu
Keyword(s):  
Colon Cancer ◽  
Steady State ◽  
Cancer Cells ◽  
Thymidylate Synthase ◽  
Colon Cancer Cells ◽  
Down Regulation

scholarly journals Differential Mechanism of ATP Production Occurs in Response to Succinylacetone in Colon Cancer Cells

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3575 ◽  
Author(s):  
Lee ◽  
Woo ◽  
Yoo ◽  
Cho ◽  
Kim
Keyword(s):  
Reactive Oxygen Species ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Oxygen Species ◽  
Colon Cancer Cells ◽  
Atp Production ◽  
Ht29 Cells ◽  
Differential Mechanism ◽  
Hct116 Cells

Our aim was to verify the potential ability of succinylacetone (SA) to inhibit mitochondrial function, thereby suppressing cancer cell proliferation. SA treatment caused apoptosis in HCT116 and HT29 cells, but not in SW480 cells, with mitochondria playing a key role. We checked for dysfunctional mitochondria after SA treatment. Mitochondria of HT29 cells were swollen, indicating damage, whereas in HCT116 cells, several mitochondria had a diminished size. Damaged mitochondria decreased ATP production and induced reactive oxygen species (ROS) in the cells. To understand SA-induced reduction in ATP production, we investigated the electron transfer chains (ETC) and pyruvate dehydrogenase kinase (PDK) activity, which prevents the transfer of acetyl-CoA to the TCA (tricarboxylic acid) cycle by inhibiting PDH (pyruvate dehydrogenase) activity. In each cell line, the inhibitory mechanism of ATP by SA was different. The activity of complex III consisting of the mitochondrial ETCs in HT29 cells was decreased. In contrast, PDH activity in HCT116 cells was reduced. Nicotinamide nucleotide transhydrogenase (NNT)-removing reactive oxygen species (ROS) was upregulated in HT29 cells, but not in HCT116 cells, indicating that in HT29 cells, a defense mechanism was activated against ROS. Collectively, our study showed a differential mechanism occurs in response to SA in colon cancer cells.

Modification of the sensitivity to cisplatin with c-myc over-expression or down-regulation in colon cancer cells

2001 ◽  
Vol 12 (10) ◽  
pp. 829-834 ◽  
Author(s):  
Tadao Funato ◽  
Kanoko Kozawa ◽  
Mitsuo Kaku ◽  
Takeshi Sasaki
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
Down Regulation ◽  
Over Expression
Sign in / Sign up

Export Citation Format

Share Document