scholarly journals Histone deacetylase inhibitors and aspirin interact synergistically to induce cell death in ovarian cancer cells

2008 ◽  
Author(s):  
Jürgen Sonnemann ◽  
Isabel Hüls ◽  
Michael Sigler ◽  
Chithra Palani ◽  
Le Hong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Ovarian Cancer Cells ◽  
Induce Cell Death

scholarly journals C-terminal binding protein-2 regulates response of epithelial ovarian cancer cells to histone deacetylase inhibitors

Oncogene ◽  
2012 ◽  
Vol 32 (33) ◽  
pp. 3896-3903 ◽  
Author(s):  
L Barroilhet ◽  
J Yang ◽  
K Hasselblatt ◽  
R M Paranal ◽  
S-K Ng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Binding Protein ◽  
Ovarian Cancer Cells

scholarly journals Histone Deacetylase Inhibitors Downregulate Checkpoint Kinase 1 Expression to Induce Cell Death in Non-Small Cell Lung Cancer Cells

PLoS ONE ◽  
2010 ◽  
Vol 5 (12) ◽  
pp. e14335 ◽  
Author(s):  
William Brazelle ◽  
Jenny M. Kreahling ◽  
Jennifer Gemmer ◽  
Yihong Ma ◽  
W. Douglas Cress ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Induce Cell Death ◽  
Checkpoint Kinase 1

Telomerase expression and cell proliferation in ovarian cancer cells induced by histone deacetylase inhibitors

2007 ◽  
Vol 277 (1) ◽  
pp. 15-19 ◽  
Author(s):  
Kun Zhu ◽  
Danni Qu ◽  
Takanori Sakamoto ◽  
Ichio Fukasawa ◽  
Masatoshi Hayashi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Ovarian Cancer Cells

scholarly journals Quinacrine-Induced Autophagy in Ovarian Cancer Triggers Cathepsin-L Mediated Lysosomal/Mitochondrial Membrane Permeabilization and Cell Death

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2004
Author(s):  
Prabhu Thirusangu ◽  
Christopher L. Pathoulas ◽  
Upasana Ray ◽  
Yinan Xiao ◽  
Julie Staub ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cytochrome C ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Cathepsin L ◽  
Membrane Permeabilization ◽  
Apoptotic Cell Death ◽  
Ovarian Cancer Cells ◽  
Autophagic Flux

We previously reported that the antimalarial compound quinacrine (QC) induces autophagy in ovarian cancer cells. In the current study, we uncovered that QC significantly upregulates cathepsin L (CTSL) but not cathepsin B and D levels, implicating the specific role of CTSL in promoting QC-induced autophagic flux and apoptotic cell death in OC cells. Using a Magic Red® cathepsin L activity assay and LysoTracker red, we discerned that QC-induced CTSL activation promotes lysosomal membrane permeability (LMP) resulting in the release of active CTSL into the cytosol to promote apoptotic cell death. We found that QC-induced LMP and CTSL activation promotes Bid cleavage, mitochondrial outer membrane permeabilization (MOMP), and mitochondrial cytochrome-c release. Genetic (shRNA) and pharmacological (Z-FY(tBU)-DMK) inhibition of CTSL markedly reduces QC-induced autophagy, LMP, MOMP, apoptosis, and cell death; whereas induced overexpression of CTSL in ovarian cancer cell lines has an opposite effect. Using recombinant CTSL, we identified p62/SQSTM1 as a novel substrate of CTSL, suggesting that CTSL promotes QC-induced autophagic flux. CTSL activation is specific to QC-induced autophagy since no CTSL activation is seen in ATG5 knockout cells or with the anti-malarial autophagy-inhibiting drug chloroquine. Importantly, we showed that upregulation of CTSL in QC-treated HeyA8MDR xenografts corresponds with attenuation of p62, upregulation of LC3BII, cytochrome-c, tBid, cleaved PARP, and caspase3. Taken together, the data suggest that QC-induced autophagy and CTSL upregulation promote a positive feedback loop leading to excessive autophagic flux, LMP, and MOMP to promote QC-induced cell death in ovarian cancer cells.

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