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JNK inhibitors ovarian cancer

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https://www.readbyqxmd.com/read/28885729/leptin-induces-matrix-metalloproteinase-7-expression-to-promote-ovarian-cancer-cell-invasion-by-activating-erk-and-jnk-pathways
#1
Ahmad Ghasemi, Seyed Isaac Hashemy, Mahmoud Aghaei, Mojtaba Panjehpour
Leptin, an adipokine secreted by adipose tissue, induces cell invasion and metastasis. MMP7 is a member of the matrix metalloproteinase family that plays an important role in cell invasion. Here we evaluate the possible role and underlying mechanism of MMP7 in the leptin- mediated cell invasion in ovarian cancer cell lines. All experiments were carried out in cultured SKOV3, OVCAR3 and CaoV-3 ovarian cell lines. MMP7 expression was determined using the western blot following treatment to various concentrations of leptin for defined time intervals...
September 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28757353/osmotic-and-heat-stress-dependent-regulation-of-mlk4%C3%AE-and-mlk3-by-the-chip-e3-ligase-in-ovarian-cancer-cells
#2
Natalya A Blessing, Srimathi Kasturirangan, Evan M Zink, April L Schroyer, Deborah N Chadee
Mixed Lineage Kinase 3 (MLK3), a member of the MLK subfamily of protein kinases, is a mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) that activates MAPK signalling pathways and regulates cellular responses such as proliferation, invasion and apoptosis. MLK4β, another member of the MLK subfamily, is less extensively studied, and the regulation of MLK4β by stress stimuli is not known. In this study, the regulation of MLK4β and MLK3 by osmotic stress, thermostress and heat shock protein 90 (Hsp90) inhibition was investigated in ovarian cancer cells...
November 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28633436/membrane-androgen-receptor-zip9-induces-croaker-ovarian-cell-apoptosis-via-stimulatory-g-protein-alpha-subunit-and-map-kinase-signaling
#3
Aubrey Converse, Chenan Zhang, Peter Thomas
Recent studies show that androgen-induced apoptosis in Atlantic croaker primary granulosa and theca (G/T) cells and in human breast and prostate cancer cell lines is mediated by the membrane androgen receptor ZIP9, which belongs to the SLC39A zinc transporter family. However, the apoptotic signaling pathways remain unclear because ZIP9 activates an inhibitory G protein in human cancer cells, whereas recombinant croaker ZIP9 activates a stimulatory G protein (Gs) in transfected cancer cells. We investigated androgen-dependent apoptotic pathways to identify the signaling pathways regulated through wild-type croaker ZIP9 in ovarian follicle cells...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28387244/the-apoptotic-mechanisms-of-mt-6-a-mitotic-arrest-inducer-in-human-ovarian-cancer-cells
#4
Mei-Chuan Chen, Yi-Chiu Kuo, Chia-Ming Hsu, Yi-Lin Chen, Chien-Chang Shen, Che-Ming Teng, Shiow-Lin Pan
Patients with ovarian cancer are typically diagnosed at an advanced stage, resulting in poor prognosis since there are currently no effective early-detection screening tests for women at average-risk for ovarian cancer. Here, we investigated the effects of MT-6, a derivative of moscatilin, in ovarian cancer cells. Our investigation showed that MT-6 inhibited the proliferation and viability of ovarian cancer cells with submicromolar IC50 values. MT-6-treated SKOV3 cells showed significant cell cycle arrest at G2/M phase, followed by an increase in the proportion of cells in a sub-G1 phase...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28277616/-e-2-methoxy-4-3-4-methoxyphenyl-prop-1-en-1-yl-phenol-suppresses-ovarian-cancer-cell-growth-via-inhibition-of-erk-and-stat3
#5
Jie Zheng, Dong Ju Son, Hye Lim Lee, Hee Pom Lee, Tae Hoon Kim, Jung Heun Joo, Young Wan Ham, Wun Jae Kim, Jae Kyung Jung, Sang-Bae Han, Jin Tae Hong
In the present study, we synthesized several non-aldehyde analogues of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal which showed anti-cancer effect. Interestingly, among the 16 compounds, we found that (E)-2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol (MMPP) showed the most significant anti-proliferative effect on PA-1 and SK-OV-3 ovarian epithelial cancer cells. MMPP treatment (0-15 µg/mL) induced apoptotic cell death, enhanced the expression of cleaved caspase-3, and cleaved caspase-9 in a concentration dependent manner...
September 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28101169/role-of-wnt-%C3%AE-catenin-wnt-c-jun-n-terminal-kinase-and-wnt-ca-2-pathways-in-cisplatin-induced-chemoresistance-in-ovarian-cancer
#6
Lu Huang, Ye Jin, Shujun Feng, Yuqing Zou, Sainan Xu, Shuang Qiu, Ling Li, Jianhua Zheng
The aim of the present study was to explore the expression of Wnt signaling proteins β-catenin, c-Jun N-terminal kinase (JNK) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in ovarian cancer cells, and assess the correlation between this expression and cisplatin-induced chemoresistance. SKOV3 ovarian carcinoma cells and SKOV3/DDP (cisplatin resistant) cells were treated with cisplatin in the absence or presence of a Wnt signaling activator (CHIR-99021, glycogen synthase kinase 3β inhibitor) or inhibitor (XAV-939, tankyrase inhibitor)...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28098862/rhein-suppresses-matrix-metalloproteinase-production-by-regulating-the-rac1-ros-mapk-ap-1-pathway-in-human-ovarian-carcinoma-cells
#7
Guomei Zhou, Fenghui Peng, Yanping Zhong, Yanhua Chen, Min Tang, Danrong Li
Matrix metalloproteinases (MMPs) are a family of calcium-dependent zinc-containing endopeptidases, which play an integral role in migration and invasion of ovarian cancer. Rac1 proteins might mostly influence cell migration and invasion by generating endogenous reactive oxygen species. Therefore, inhibiting MMPs and regulating the Rac1/ROS/MAPK/AP-1 pathway may be a new therapeutic strategy for ovarian cancer. In this study, we found that rhein could suppress the invasion and migration of SKOV3-PM4 cells with characteristics of directional highly lymphatic metastasis...
March 2017: International Journal of Oncology
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
#8
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
#9
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...
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
#10
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...
September 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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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