scholarly journals Caspase-mediated Cleavage of β-Catenin Precedes Drug-induced Apoptosis in Resistant Cancer Cells

2009 ◽  
Vol 284 (20) ◽  
pp. 13577-13588 ◽  
Author(s):  
Subramanian Senthivinayagam ◽  
Prajna Mishra ◽  
Suresh Kanna Paramasivam ◽  
Srinivas Yallapragada ◽  
Malay Chatterjee ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Drug Induced ◽  
Induced Apoptosis

scholarly journals Contribution of Mitochondrial Ion Channels to Chemo-Resistance in Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 761 ◽  
Author(s):  
Roberta Peruzzo ◽  
Ildiko Szabo
Keyword(s):  
Ion Channels ◽  
Cytochrome C ◽  
Cancer Cells ◽  
Cytochrome C Release ◽  
Drug Induced ◽  
Point Of No Return ◽  
Different Types ◽  
Subsequent Activation ◽  
Induced Apoptosis ◽  
Potential Efficiency

Mitochondrial ion channels are emerging oncological targets, as modulation of these ion-transporting proteins may impact on mitochondrial membrane potential, efficiency of oxidative phosphorylation and reactive oxygen production. In turn, these factors affect the release of cytochrome c, which is the point of no return during mitochondrial apoptosis. Many of the currently used chemotherapeutics induce programmed cell death causing damage to DNA and subsequent activation of p53-dependent pathways that finally leads to cytochrome c release from the mitochondrial inter-membrane space. The view is emerging, as summarized in the present review, that ion channels located in this organelle may account in several cases for the resistance that cancer cells can develop against classical chemotherapeutics, by preventing drug-induced apoptosis. Thus, pharmacological modulation of these channel activities might be beneficial to fight chemo-resistance of different types of cancer cells.

Human U3 protein 14a plays an anti-apoptotic role in cancer cells

2017 ◽  
Vol 398 (11) ◽  
pp. 1247-1257 ◽  
Author(s):  
Teng Ma ◽  
Chenxi Lu ◽  
Yafei Guo ◽  
Chunfeng Zhang ◽  
Xiaojuan Du
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Protein Level ◽  
Tumor Therapy ◽  
Caspase Inhibitor ◽  
Chemotherapeutic Drug ◽  
Intrinsic Pathway ◽  
Down Regulation ◽  
Drug Induced ◽  
Induced Apoptosis

AbstractHuman U three protein 14a (hUTP14a) binds p53 and promotes p53 degradation. Here, we report that hUTP14a plays an anti-apoptotic role in tumor cells through a p53-independent pathway. Knockdown of hUTP14a activated the intrinsic pathway of apoptosis and sensitized tumor cells to chemotherapeutic drug-induced apoptosis. In addition, the protein level of hUTP14a decreased upon chemotherapeutic drug- or irradiation-induced apoptosis. Importantly, the decrease of hUTP14a during induced apoptosis was not blocked by pan-caspase inhibitor z-VAD-FMK, indicating that the down-regulation of hUTP14a is an upstream event in apoptosis. Furthermore, ectopically expressed hUTP14a protected tumor cells from chemotherapeutic drug-induced apoptosis. In summary, our data showed that hUTP14a protected tumor cells from chemotherapeutic drug-induced apoptosis and thus might possess a potential as a target for anti-tumor therapy.

scholarly journals Cinnamaldehyde Derivative (CB-PIC) Sensitizes Chemo-Resistant Cancer Cells to Drug-Induced Apoptosis via Suppression of MDR1 and its Upstream STAT3 and AKT Signalling

2015 ◽  
Vol 35 (5) ◽  
pp. 1821-1830 ◽  
Author(s):  
Jianzhong Xi ◽  
Miyong Yun ◽  
Duckgue Lee ◽  
Moon-Nyeo Park ◽  
Eun-Ok Kim ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Epigallocatechin Gallate ◽  
Resistant Cell ◽  
Functional Assay ◽  
Drug Resistant ◽  
Transport Activity ◽  
Drug Induced ◽  
P Glycoprotein ◽  
Induced Apoptosis ◽  
Intracellular Region

Background/Aims: Our group reported that cinnamaldehyde derivative, (E)-4-((2-(3-oxopop-1-enyl)phenoxy)methyl)pyridinium malonic acid (CB-PIC) induced apoptosis in hypoxic SW620 colorectal cancer cells via activation of AMP-activated protein kinase (AMPK) and extracellular signal regulated kinase (ERK). Herein, sensitizing effect of CB-PIC was investigated in resistant cancer cells such as paclitaxel (PT) resistant lung cancer cells (H460/PT), and Adriamycin (Adr) resistant breast cancer (MCF7/Adr) and colon cancer (HCT15/cos) cells. Methods: Various drug resistant cell lines were treated with CB-PIC, and the signalling pathway and functional assay were explored by Western blot, Rhodamine assay, FACS, RT-PCR and MTT assay. Results: We found that CB-PIC effectively exerted cytotoxicity, increased sub G1 population and the cleaved form of poly (ADP-ribose) polymerase (PARP) and caspase 9 in drug resistant cancer cells. Furthermore, CB-PIC sensitized resistant cancer cells to adriamycin via downregulation of survival proteins such as survivin, Bcl-xL and Bcl-2, along with MDR1 suppression leading to accumulation of drug in the intracellular region. Of note, CB-PIC transcriptionally decreased MDR1 expression via suppression of STAT3 and AKT signalling in three resistant cancer cells with highly expressed P-glycoprotein. Nonetheless, CB-PIC did not affect transport activity of P-glycoprotein in a short time efflux assay, while epigallocatechin gallate (EGCG) accumulated Rhodamine 123 into intracellular region of cell by direct inhibition of MDR1 transport activity. Conclusions: These data demonstrate that CB-PIC suppresses the P-glycoprotein expression through inhibition of STAT3 and AKT signalling to overcome drug resistance in chemo-resistant cancer cells as a potent chemotherapeutic sensitizer.

scholarly journals A Potential Role of Nuclear Matrix-associated Protein Kinase CK2 in Protection against Drug-induced Apoptosis in Cancer Cells

2000 ◽  
Vol 276 (8) ◽  
pp. 5992-5999 ◽  
Author(s):  
Chuanhai Guo ◽  
Shihui Yu ◽  
Alan T. Davis ◽  
Huamin Wang ◽  
Jeffrey E. Green ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cancer Cells ◽  
Nuclear Matrix ◽  
Protein Kinase Ck2 ◽  
Potential Role ◽  
Drug Induced ◽  
Induced Apoptosis ◽  
Kinase Ck2 ◽  
Apoptosis In Cancer Cells
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