scholarly journals WWOX sensitises ovarian cancer cells to paclitaxel via modulation of the ER stress response

2017 ◽  
Vol 8 (7) ◽  
pp. e2955-e2955 ◽  
Author(s):  
Szymon Janczar ◽  
Jaya Nautiyal ◽  
Yi Xiao ◽  
Edward Curry ◽  
Mingjun Sun ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stress Response ◽  
Er Stress ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Er Stress Response

scholarly journals Targeting the IRE1α/XBP1s pathway suppresses CARM1-expressing ovarian cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianhuang Lin ◽  
Heng Liu ◽  
Takeshi Fukumoto ◽  
Joseph Zundell ◽  
Qingqing Yan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stress Response ◽  
Er Stress ◽  
Cancer Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Er Stress Response

AbstractCARM1 is often overexpressed in human cancers including in ovarian cancer. However, therapeutic approaches based on CARM1 expression remain to be an unmet need. Cancer cells exploit adaptive responses such as the endoplasmic reticulum (ER) stress response for their survival through activating pathways such as the IRE1α/XBP1s pathway. Here, we report that CARM1-expressing ovarian cancer cells are selectively sensitive to inhibition of the IRE1α/XBP1s pathway. CARM1 regulates XBP1s target gene expression and directly interacts with XBP1s during ER stress response. Inhibition of the IRE1α/XBP1s pathway was effective against ovarian cancer in a CARM1-dependent manner both in vitro and in vivo in orthotopic and patient-derived xenograft models. In addition, IRE1α inhibitor B-I09 synergizes with immune checkpoint blockade anti-PD1 antibody in an immunocompetent CARM1-expressing ovarian cancer model. Our data show that pharmacological inhibition of the IRE1α/XBP1s pathway alone or in combination with immune checkpoint blockade represents a therapeutic strategy for CARM1-expressing cancers.

scholarly journals Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0189524 ◽  
Author(s):  
Mian M. K. Shahzad ◽  
Mildred Felder ◽  
Kai Ludwig ◽  
Hannah R. Van Galder ◽  
Matthew L. Anderson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Linoleic Acid ◽  
Er Stress ◽  
Cancer Cells ◽  
Conjugated Linoleic Acid ◽  
Ovarian Cancer Cells ◽  
And Migration ◽  
Proliferation And Migration

Highly cytotoxic gold(i)-phosphane dithiocarbamate complexes trigger an ER stress-dependent immune response in ovarian cancer cells

2020 ◽  
Vol 49 (22) ◽  
pp. 7355-7363 ◽  
Author(s):  
Hai Van Le ◽  
Maria V. Babak ◽  
Muhammad Ali Ehsan ◽  
Muhammad Altaf ◽  
Lisa Reichert ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Immune System ◽  
Er Stress ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
System P ◽  
Stress Dependent

Highly cytotoxic AuI-dithiocarbamate complexes were designed to induce severe integrative stress in ovarian cancer cells, leading to the surface exposure of calreticulin, which is a first step in the activation of immune system.

scholarly journals TRPV1 Antagonist DWP05195 Induces ER Stress-Dependent Apoptosis through the ROS-p38-CHOP Pathway in Human Ovarian Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1702 ◽  
Author(s):  
Yi-Yue Wang ◽  
Kyung-Tae Lee ◽  
Myong Cheol Lim ◽  
Jung-Hye Choi
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Er Stress ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Chop Expression ◽  
Anti Cancer ◽  
Trpv1 Antagonist ◽  
Induced Apoptosis

In addition to their analgesic activity, transient receptor potential vanilloid 1 (TRPV1) agonists and antagonists demonstrate profound anti-cancer activities in various human cancers. In the present study, we investigated the anti-cancer activity of a novel TRPV1 antagonist, DWP05195, and evaluated its molecular mechanism in human ovarian cancer cells. DWP05195 demonstrated potent growth inhibitory effects in all five ovarian cancer cell lines examined. DWP05195 induced apoptosis through the activation of caspase-3, -8, and -9. DWP05195 induced C/EBP homologous protein (CHOP) expression and endoplasmic reticulum (ER) stress. Sodium phenylbutyrate (4-PBA), an ER-stress inhibitor, and CHOP knockdown significantly suppressed DWP5195-induced cell death. DWP05195-enhanced CHOP expression stimulated intrinsic and extrinsic apoptotic pathways through the regulation of Bcl2-like11 (BIM), death receptor 4 (DR4), and DR5. DWP05195-induced cell death was associated with increased reactive oxygen species (ROS) levels and p38 pathway activation. Pre-treatment with the antioxidant N-acetyl-L-cysteine (NAC) significantly suppressed DWP05195-induced CHOP expression and p38 activation. Inhibition of NADPH oxidase (NOX) through p47phox knockdown abolished DWP05195-induced CHOP expression and cell death. Taken together, the findings indicate that DWP05195 induces ER stress-induced apoptosis via the ROS-p38-CHOP pathway in human ovarian cancer cells.

scholarly journals JI017, a Complex Herbal Medication, Induces Apoptosis via the Nox4–PERK–CHOP Axis in Ovarian Cancer Cells

2021 ◽  
Vol 22 (22) ◽  
pp. 12264
Author(s):  
Tae Woo Kim ◽  
Seong-Gyu Ko
Keyword(s):  
Ovarian Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Cancer Cells ◽  
Combination Treatment ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Diphenylene Iodonium ◽  
Anti Cancer

Many anti-cancer drugs, including paclitaxel and etoposide, have originated and been developed from natural products, and traditional herbal medicines have fewer adverse effects and lesser toxicity than anti-tumor reagents. Therefore, we developed a novel complex herbal medicine, JI017, which mediates endoplasmic reticulum (ER) stress and apoptosis through the Nox4–PERK–CHOP signaling pathway in ovarian cancer cells. JI017 treatment increases the expression of GRP78, ATF4, and CHOP and the phosphorylation of PERK and eIF2α via the upregulation of Nox4. Furthermore, it increases the release of intracellular reactive oxygen species (ROS), the production of intracellular Ca2+, and the activation of exosomal GRP78 and cell lysate GRP78. Combination treatment using the sarco/endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin (TG) and JI017 reportedly induces increased ER stress and cell death in comparison to the control; however, knockdown experiments of PERK and CHOP indicated suppressed apoptosis and ER stress in JI017-treated ovarian cancer cells. Furthermore, targeting Nox4 using specific siRNA and pharmacological ROS inhibitors, including N-acetylcystein and diphenylene iodonium, blocked apoptosis and ER stress in JI017-treated ovarian cancer cells. In the radioresistant ovarian cancer model, when compared to JI017 alone, JI017 co-treatment with radiation induced greater cell death and resulted in overcoming radioresistance by inhibiting epithelial–mesenchymal-transition-related phenomena such as the reduction of E-cadherin and the increase of N-cadherin, vimentin, Slug, and Snail. These findings suggest that JI017 is a powerful anti-cancer drug for ovarian cancer treatment and that its combination treatment with radiation may be a novel therapeutic strategy for radioresistant ovarian cancer.

Sign in / Sign up

Export Citation Format

Share Document