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JNK inhibitors ovarian cancer

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https://www.readbyqxmd.com/read/27904682/targeting-cancer-cell-metabolism-the-combination-of-metformin-and-2-deoxyglucose-regulates-apoptosis-in-ovarian-cancer-cells-via-p38-mapk-jnk-signaling-pathway
#1
Jie Zhu, Ya Zheng, Haiyan Zhang, Hong Sun
Targeting cancer cell metabolism is a new promising strategy to fight cancer. Metformin, a first-line treatment for type 2 diabetes mellitus, exerts anti-cancer and anti-proliferative action. 2-deoxyglucose (2-DG), a glucose analog, works as a competitive inhibitor of glycolysis. In this study, we show for the first time that metformin in combination with 2-DG inhibited growth, migration, invasion and induced cell cycle arrest of ovarian cancer cells in vitro. Moreover, metformin and 2-DG could efficiently induce apoptosis in ovarian cancer cells, which was achieved by activating p38 MAPK and JNK pathways...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27848251/allergen-removed-rhus-verniciflua-extract-induces-ovarian-cancer-cell-death-via-jnk-activation
#2
Se-Hui Kang, In-Hu Hwang, Eunju Son, Chong-Kwan Cho, Jong-Soon Choi, Soo-Jung Park, Byeong-Churl Jang, Kyung-Bok Lee, Zee-Won Lee, Jong Hoon Lee, Hwa-Seung Yoo, Ik-Soon Jang
Nuclear factor-[Formula: see text]B (NF-[Formula: see text]B)/Rel transcription factors are best known for their central roles in promoting cell survival in cancer. NF-[Formula: see text]B antagonizes tumor necrosis factor (TNF)-[Formula: see text]-induced apoptosis through a process involving attenuation of the c-Jun-N-terminal kinase (JNK). However, the role of JNK activation in apoptosis induced by negative regulation of NF-[Formula: see text]B is not completely understood. We found that allergen-removed Rhus verniciflua Stokes (aRVS) extract-mediated NF-[Formula: see text]B inhibition induces apoptosis in SKOV-3 ovarian cancer cells via the serial activation of caspases and SKOV-3 cells are most specifically suppressed by aRVS...
November 16, 2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27032907/eclalbasaponin-ii-induces-autophagic-and-apoptotic-cell-death-in-human-ovarian-cancer-cells
#3
Yoon Jin Cho, Jeong-Hwa Woo, Jae-Seung Lee, Dae Sik Jang, Kyung-Tae Lee, Jung-Hye Choi
Triterpenoids echinocystic acid and its glycosides, isolated from several Eclipta prostrata, have been reported to possess various biological activities such as anti-inflammatory, anti-bacterial, and anti-diabetic activity. However, the cytotoxicity of the triterpenoids in human cancer cells and their molecular mechanism of action are poorly understood. In the present study, we found that eclalbasaponin II with one glucose moiety has potent cytotoxicity in three ovarian cancer cells and two endometrial cancer cells compared to an aglycone echinocystic acid and eclalbasaponin I with two glucose moiety...
February 27, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27027242/the-novel-jnk-inhibitor-as602801-inhibits-cancer-stem-cells-in-vitro-and-in-vivo
#4
Masashi Okada, Kenta Kuramoto, Hiroyuki Takeda, Hikaru Watarai, Hirotsugu Sakaki, Shizuka Seino, Manabu Seino, Shuhei Suzuki, Chifumi Kitanaka
A phase 2 clinical trial investigating the efficacy and safety of AS602801, a newly developed JNK inhibitor, in the treatment of inflammatory endometriosis is complete. We are now examining whether AS602801 acts against human cancer cells in vitro and in vivo. In vitro, AS602801 exhibited cytotoxicity against both serum-cultured non-stem cancer cells and cancer stem cells derived from human pancreatic cancer, non-small cell lung cancer, ovarian cancer and glioblastoma at concentrations that did not decrease the viability of normal human fibroblasts...
May 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/26918450/a-nuclear-directed-human-pancreatic-ribonuclease-pe5-targets-the-metabolic-phenotype-of-cancer-cells
#5
Anna Vert, Jessica Castro, Marc Ribó, Antoni Benito, Maria Vilanova
Ribonucleases represent a new class of antitumor RNA-damaging drugs. However, many wild-type members of the vertebrate secreted ribonuclease family are not cytotoxic because they are not able to evade the cytosolic ribonuclease inhibitor. We previously engineered the human pancreatic ribonuclease to direct it to the cell nucleus where the inhibitor is not present. The best characterized variant is PE5 that kills cancer cells through apoptosis mediated by the p21(WAF1/CIP1) induction and the inactivation of JNK...
April 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/26902409/evodiamine-from-evodia-rutaecarpa-induces-apoptosis-via-activation-of-jnk-and-perk-in-human-ovarian-cancer-cells
#6
Tze-Chien Chen, Chih-Chiang Chien, Ming-Shun Wu, Yen-Chou Chen
BACKGROUND: Evodiamine (EVO; 8,13,13b,14-tetrahydro-14-methylindolo[2'3'-3,4]pyrido[2,1-b]quinazolin-5-[7H]-one derived from the traditional herbal medicine Evodia rutaecarpa was reported to possess anticancer activity; however, the anticancer mechanism of EVO against the viability of human ovarian cancer cells is still unclear. PURPOSE: A number of studies showed that chemotherapeutic benefits may result from targeting the endoplasmic reticular (ER) stress signaling pathway...
January 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/26840702/ghrelin-attenuates-the-growth-of-ho-8910-ovarian-cancer-cells-through-the-erk-pathway
#7
R X Bai, W P Wang, P W Zhao, C B Li
Ovarian cancer is one of the most common causes of death from gynecologic tumors and is an important public health issue. Ghrelin is a recently discovered bioactive peptide that acts as a natural endogenous ligand of the growth hormone secretagogue receptor (GHSR). Several studies have identified the protective effects of ghrelin on the mammalian reproductive system. However, little research has been done on the effects of ghrelin on ovarian cancer cells, and the underlying mechanisms of these effects. We sought to understand the potential involvement of mitogen-activated protein kinases (MAPKs) in ghrelin-mediated inhibition of growth of the ovarian line HO-8910...
March 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/26824454/placental-growth-factor-promotes-ovarian-cancer-cell-invasion-via-zeb2
#8
Ning Song, Hao Liu, Xiaoxin Ma, Shulan Zhang
BACKGROUND/AIMS: The aggressive manner of ovarian cancer (OVC) cells accounts for the majority of its lethality. Recently, we have shown that placental growth factor (PLGF) promotes metastases of OVC cells through miR-543-regulated MMP7. In the current study, we analyzed the effects of PLGF on another cell invasion associated protein, ZEB2, in OVC cells. METHODS: The PLGF and ZEB2 levels in OVC tissues were compared to the paired adjacent non-tumor ovary tissue...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/26740585/kinase-signalling-pathways-in-endometriosis-potential-targets-for-non-hormonal-therapeutics
#9
REVIEW
Brett D McKinnon, Vida Kocbek, Kostantinos Nirgianakis, Nick A Bersinger, Michael D Mueller
BACKGROUND: Endometriosis, the growth of endometrial tissue outside the uterine cavity, is associated with chronic pelvic pain, subfertility and an increased risk of ovarian cancer. Current treatments include the surgical removal of the lesions or the induction of a hypoestrogenic state. However, a reappearance of the lesion after surgery is common and a hypoestrogenic state is less than optimal for women of reproductive age. Additional approaches are required. Endometriosis lesions exist in a unique microenvironment characterized by increased concentrations of hormones, inflammation, oxidative stress and iron...
April 2016: Human Reproduction Update
https://www.readbyqxmd.com/read/26716645/carnitine-palmitoyltransferase-1a-functions-to-repress-foxo-transcription-factors-to-allow-cell-cycle-progression-in-ovarian-cancer
#10
Huanjie Shao, Esraa M Mohamed, Guoyan G Xu, Michael Waters, Kai Jing, Yibao Ma, Yan Zhang, Sarah Spiegel, Michael O Idowu, Xianjun Fang
Cancer cells rely on hyperactive de novo lipid synthesis for maintaining malignancy. Recent studies suggest involvement in cancer of fatty acid oxidation, a process functionally opposite to lipogenesis. A mechanistic link from lipid catabolism to oncogenic processes is yet to be established. Carnitine palmitoyltransferase 1 (CPT1) is a rate-limiting enzyme of fatty acid β-oxidation (FAO) that catalyzes the transfer of long-chain acyl group of the acyl-CoA ester to carnitine, thereby shuttling fatty acids into the mitochondrial matrix for β-oxidation...
January 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/26549707/nilotinib-reduced-the-viability-of-human-ovarian-cancer-cells-via-mitochondria-dependent-apoptosis-independent-of-jnk-activation
#11
Tze-Chien Chen, Ming-Chih Yu, Chih-Chiang Chien, Ming-Shun Wu, Yu-Chieh Lee, Yen-Chou Chen
Nilotinib (AMN) induces apoptosis in various cancer cells; however the effect of AMN on human ovarian cancer cells is still unclear. A reduction in cell viability associated with the occurrence of apoptotic characteristics was observed in human SKOV-3 ovarian cancer cells under AMN but not sorafenib (SORA) or imatinib (STI) stimulation. Activation of apoptotic pathway including increased caspase (Casp)-3 and poly(ADP-ribose) polymerase 1 (PARP1) protein cleavage by AMN was detected with disrupted mitochondrial membrane potential (MMP) accompanied by decreased Bcl-2 protein and increased cytosolic cytochrome (Cyt) c/cleaved Casp-9 protein expressions was found, and AMN-induced cell death was inhibited by peptidyl Casp inhibitors, VAD, DEVD and LEHD...
March 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/26534836/time-staggered-inhibition-of-jnk-effectively-sensitizes-chemoresistant-ovarian-cancer-cells-to-cisplatin-and-paclitaxel
#12
Manabu Seino, Masashi Okada, Hirotsugu Sakaki, Hiroyuki Takeda, Hikaru Watarai, Shuhei Suzuki, Shizuka Seino, Kenta Kuramoto, Tsuyoshi Ohta, Satoru Nagase, Hirohisa Kurachi, Chifumi Kitanaka
Ovarian cancer is the most lethal gynecological malignancy, for which platinum- and taxane-based chemotherapy plays a major role. Chemoresistance of ovarian cancer poses a major obstacle to the successful management of this devastating disease; however, effective measures to overcome platinum and taxane resistance are yet to be established. In the present study, while investigating the mechanism underlying the chemoresistance of ovarian cancer, we found that JNK may have a key role in the resistance of ovarian cancer cells to cisplatin and paclitaxel...
January 2016: Oncology Reports
https://www.readbyqxmd.com/read/26433471/interleukin-33-predicts-poor-prognosis-and-promotes-ovarian-cancer-cell-growth-and-metastasis-through-regulating-erk-and-jnk-signaling-pathways
#13
Xiaoguang Tong, Mark Barbour, Kezuo Hou, Chao Gao, Shuang Cao, Jingli Zheng, Yang Zhao, Rong Mu, Hui-Rong Jiang
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, it remains a huge challenge to understand the cellular and molecular mechanisms of the aggressive behavior of EOC cells. Here we investigated the role of an immunomodulatory cytokine IL-33 and its receptor ST2 in mediating the growth and metastasis of EOC. Our data show that both IL-33 and ST2 were highly up-regulated in EOC tumors compared with normal ovary and ovarian benign tumors, and the expression levels were further increased in tumor tissues at the metastatic site...
January 2016: Molecular Oncology
https://www.readbyqxmd.com/read/26261528/unfolded-protein-response-mediated-jnk-ap-1-signal-transduction-a-target-for-ovarian-cancer-treatment
#14
Gao-Feng Zheng, Zhen Cai, Xiang-Kai Meng, Yi Zhang, Wei Zhu, Xiao-Yan Pang, Lei Dou
Researches have revealed several stressors, which could activate unfolded protein response (UPR) in cells. However, the survival or death pathway was determined by the duration of UPR exposure. Based on the UPR mediated death pathway, our study was aimed to investigate role of UPR on c-Jun N-terminal kinase (JNK)/activator protein-1 (Ap-1) signal transduction in diindolylmethane (DIM) treated ovarian cancer cell lines. Activation of UPR proteins, UPR mediated apoptotic signaling proteins and expression level of EpCAM, JNK, Ap-1, Caspase-3 and Bcl-2 were measured...
2015: International Journal of Clinical and Experimental Pathology
https://www.readbyqxmd.com/read/25731856/regulation-by-heat-shock-protein-22-hspb8-of-transforming-growth-factor-%C3%AE-induced-ovary-cancer-cell-migration
#15
Mariko Suzuki, Rie Matsushima-Nishiwaki, Gen Kuroyanagi, Noriko Suzuki, Reika Takamatsu, Tatsuro Furui, Naoki Yoshimi, Osamu Kozawa, Ken-ichirou Morishige
Accumulating evidence suggests that heat shock proteins (HSPs) are implicated in progression of cancer. HSP22 (HSPB8), a small HSP, is recognized to be ubiquitously expressed in various tissues. However, the expression and the role of HSP22 in ovarian cancer remain to be clarified. In the present study, we investigated the involvement of HSP22 in transforming growth factor (TGF)-α-induced migration of ovarian cancer cells. The expression of HSP22 was detected in a serous ovarian cancer cell line, SKOV3.ip1...
April 1, 2015: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/25376608/the-protein-phosphatase-2a-inhibitor-lb100-sensitizes-ovarian-carcinoma-cells-to-cisplatin-mediated-cytotoxicity
#16
Ki-Eun Chang, Bih-Rong Wei, James P Madigan, Matthew D Hall, R Mark Simpson, Zhengping Zhuang, Michael M Gottesman
Despite early positive response to platinum-based chemotherapy, the majority of ovarian carcinomas develop resistance and progress to fatal disease. Protein phosphatase 2A (PP2A) is a ubiquitous phosphatase involved in the regulation of DNA-damage response (DDR) and cell-cycle checkpoint pathways. Recent studies have shown that LB100, a small-molecule inhibitor of PP2A, sensitizes cancer cells to radiation-mediated DNA damage. We hypothesized that LB100 could sensitize ovarian cancer cells to cisplatin treatment...
January 2015: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/25375375/bortezomib-enhances-cancer-cell-death-by-blocking-the-autophagic-flux-through-stimulating-erk-phosphorylation
#17
C Kao, A Chao, C-L Tsai, W-C Chuang, W-P Huang, G-C Chen, C-Y Lin, T-H Wang, H-S Wang, C-H Lai
The antitumor activity of an inhibitor of 26S proteasome bortezomib (Velcade) has been observed in various malignancies, including colon cancer, prostate cancer, breast cancer, and ovarian cancer. Bortezomib has been proposed to stimulate autophagy, but scientific observations did not always support this. Interactions between ERK activity and autophagy are complex and not completely clear. Autophagy proteins have recently been shown to regulate the functions of ERK, and ERK activation has been found to induce autophagy...
November 6, 2014: Cell Death & Disease
https://www.readbyqxmd.com/read/25097657/role-of-jnk-activation-and-mitochondrial-bax-translocation-in-allicin-induced-apoptosis-in-human-ovarian-cancer-skov3-cells
#18
Ling Xu, Jin Yu, Dongxia Zhai, Danying Zhang, Wei Shen, Lingling Bai, Zailong Cai, Chaoqin Yu
Background. Allicin, the major component of freshly crushed garlic, is one of the most biologically active compounds of garlic; it has been reported to induce apoptosis in cancer cells; however, the mechanism by which allicin exerts its apoptotic effects is not fully understood. The aim of the present study was to further elucidate the apoptotic pathways induced by allicin in the human ovarian cancer cell line SKOV3. Methods. Cell proliferation and apoptosis were measured by cell-counting assay and flow cytometry analysis...
2014: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/25044439/inhibition-of-jnk3-promotes-apoptosis-induced-by-bh3-mimetic-s1-in-chemoresistant-human-ovarian-cancer-cells
#19
Xiaochun Yang, Xiyan Xiang, Meihui Xia, Jing Su, Yao Wu, Luyan Shen, Ye Xu, Liankun Sun
Previous studies have suggested that the novel BH3 mimetic S1 could induce apoptosis in diverse tumor cell lines through endoplasmic reticulum (ER) stress or mitochondrial cell death pathways. The activation of c-Jun N-terminal kinase (JNK) through inositol requiring enzyme-1 (IRE1) is closely connected to ER stress-induced apoptosis. However, the role of JNK is complex, as there are different JNK subtypes and the function of each subtype is still not entirely clear. Here we found that the mRNA expression of JNK3 was continuously high in S1-treated human ovarian cancer SKOV3/DDP cells using a human unfolded protein response (UPR) pathway PCR array...
February 2015: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/25014355/identification-and-characterization-of-membrane-androgen-receptors-in-the-zip9-zinc-transporter-subfamily-ii-role-of-human-zip9-in-testosterone-induced-prostate-and-breast-cancer-cell-apoptosis
#20
Peter Thomas, Yefei Pang, Jing Dong, A Håkan Berg
Recently, we discovered a cDNA in teleost ovarian follicle cells belonging to the zinc transporter ZIP9 subfamily (SLC39A9) encoding a protein with characteristics of a membrane androgen receptor (mAR). Here, we demonstrate that human ZIP9 expressed in MDA-MB-468 breast cancer cells and stably overexpressed in human prostate cancer PC-3 cells (PC-3-ZIP9) also displays the ligand binding and signaling characteristics of a specific, high-affinity mAR. Testosterone treatment of MDA-MB-468 and PC-3-ZIP9 cells caused activation of G proteins and second messenger pathways as well as increases in intracellular free zinc concentrations that were accompanied by induction of apoptosis...
November 2014: Endocrinology
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