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JNK inhibitors ovarian cancer

Lihui Si, Ruiqi Yang, Ruixin Lin, Shuli Yang
Piperine, a kind of natural alkaloid found in the fruit of black (Piper nigrum Linn) and long (Piper longum Linn), has shown antitumor activities toward various cancer cell lines. However, the antitumor effects of piperine on ovarian cancer and the underlying mechanism are not fully elucidated. Our result showed that piperine reduced the cell viability of A2780 cells in a concentration and time-dependent manner, but has not any effect on normal ovarian cells. Flow cytometric analysis revealed that piperine suppressed cells proliferation via induction of apoptosis, which was followed by release of mitochondrial cytochrome c to cytosol, activation of caspase-3, and -9, as well as cleaved PARP...
May 1, 2018: Bioscience Reports
Prabir Kumar Chakraborty, Brennah Murphy, Soumyajit Banerjee Mustafi, Anindya Dey, Xunhao Xiong, Geeta Rao, Sarwat Naz, Min Zhang, Da Yang, Danny N Dhanasekaran, Resham Bhattacharya, Priyabrata Mukherjee
Deregulation of mitochondrial morphogenesis, a dynamic equilibrium between mitochondrial fusion and fission processes, is now evolving as a key metabolic event that fuels tumor growth and therapy resistance. However, fundamental knowledge underpinning how cancer cells reprogram mitochondrial morphogenesis remains incomplete. Here, we report that cystathionine β-synthase (CBS) reprograms mitochondrial morphogenesis in ovarian cancer (OvCa) cells by selectively regulating the stability of mitofusin 2 (MFN2)...
March 1, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Priya Samuel, Laura Ann Mulcahy, Fiona Furlong, Helen O McCarthy, Susan Ann Brooks, Muller Fabbri, Ryan Charles Pink, David Raul Francisco Carter
Ovarian cancer has a poor overall survival that is partly caused by resistance to drugs such as cisplatin. Resistance can be acquired as a result of changes to the tumour or due to altered interactions within the tumour microenvironment. Extracellular vesicles (EVs), small lipid-bound vesicles that are loaded with macromolecular cargo and released by cells, are emerging as mediators of communication in the tumour microenvironment. We previously showed that EVs mediate the bystander effect, a phenomenon in which stressed cells can communicate with neighbouring naive cells leading to various effects including DNA damage; however, the role of EVs released following cisplatin treatment has not been tested...
January 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Caihong Li, Li Hong, Cheng Liu, Jie Min, Ming Hu, Wenjun Guo
BACKGROUND: Multidrug resistance in malignant tumours hinders the treatment of tumours. Studies showed that astragalus polysaccharides (APS), one major active ingredient of astragalus, enhanced the sensitivity of non-small cell lung cancer and liver cancer cells to chemotherapeutic drug. However, the effect of APS on ovarian cancer is still unclear. In this study, we will examine the sensitizing effect of APS on SKOV3 cells to cisplatin and explore the possible mechanism. METHODS: MTT assay was employed to examine the viability of SKOV3 after treatment with APS and cisplatin...
February 2018: Archives of Gynecology and Obstetrics
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...
February 2018: Journal of Cellular Biochemistry
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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