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https://www.readbyqxmd.com/read/29156790/kaempferol-induces-autophagic-cell-death-of-hepatocellular-carcinoma-cells-via-activating-ampk-signaling
#1
Bing Han, Yi-Qun Yu, Qi-Lian Yang, Chun-Ying Shen, Xiao-Juan Wang
In the present study, we demonstrate that Kaempferol inhibited survival and proliferation of established human hepatocellular carcinoma (HCC) cell lines (HepG2, Huh-7, BEL7402, and SMMC) and primary human HCC cells. Kaempferol treatment in HCC cells induced profound AMP-activated protein kinase (AMPK) activation, which led to Ulk1 phosphorylation, mTOR complex 1 inhibition and cell autophagy. Autophagy induction was reflected by Beclin-1/autophagy gene 5 upregulation and p62 degradation as well as light chain 3B (LC3B)-I to LC3B-II conversion and LC3B puncta formation...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133128/bca3-contributes-to-the-malignant-progression-of-hepatocellular-carcinoma-through-akt-activation-and-nf-%C3%AE%C2%BAb-translocation
#2
Dong Ma, Mengquan Li, Jing Su, Shuijun Zhang
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide with elusive molecular mechanisms. The aim of this study is to investigate the clinical significance and biological roles of breast cancer-associated protein 3 (BCA3) in HCC. Our investigation demonstrated that BCA3 expression was up-regulated in primary HCC tissues, and BCA3 levels were positively correlated with tumor size, TNM stage, microvascular invasion and poor prognosis. BCA3 promoted tumor growth, metastasis and angiogenesis of HCC in vitro and in vivo...
November 10, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29112301/ribavirin-augments-doxorubicin-s-efficacy-in-human-hepatocellular-carcinoma-through-inhibiting-doxorubicin-induced-eif4e-activation
#3
Jun Tan, Jingfen Ye, Meijun Song, Mi Zhou, Yaoren Hu
Activation of eukaryotic translation initiation factor 4E (eIF4E) is a cellular survival mechanism in response to chemotherapy in cancers. In this work, we demonstrate that targeting eIF4E by ribavirin sensitizes hepatocellular carcinoma (HCC) cell response to doxorubicin. Ribavirin inhibits growth and survival of HCC cells, and to a greater extent than in normal liver cells. Its combination with doxorubicin achieves greater efficacy than single drug in vitro and in vivo. Ribavirin suppresses phosphorylation of molecules involved in Akt/mTOR/eIF4E pathway...
November 7, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29108133/targeted-delivery-of-mir-199a-3p-using-self-assembled-dipeptide-nanoparticles-efficiently-reduces-hepatocellular-carcinoma
#4
Aditi Varshney, Jiban J Panda, Avishek K Singh, Nitin Yadav, Chhagan Bihari, Subhrajit Biswas, Shiv K Sarin, Virander S Chauhan
Hepatocellular carcinoma (HCC) is an aggressive tumor with limited systemic and locoregional modalities of treatment. Although microRNA (miRNA) based therapies have significant potential, their targeted delivery remains a major challenge. miR-199a-3p functions as an important tumor suppressor in HCC, which regulates various cellular processes. Recently, peptide-based nanoparticles (NPs) have been developed to deliver oligonucleotides including miRNA. Here, we describe the synthesis and characterization of arginine α,β-dehydrophenylalanine (RΔF) nanoparticles for the selective delivery of miR-199a-3p to restore dysregulated gene expression in HCC...
November 6, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29094287/targeting-ampk-mtor-and-%C3%AE-catenin-by-combined-metformin-and-aspirin-therapy-in-hcc-an-appraisal-in-egyptian-hcc-patients
#5
Doaa Ali Abdelmonsif, Ahmed S Sultan, Wessam F El-Hadidy, Dina Mohamed Abdallah
BACKGROUND: Hepatocellular carcinoma (HCC) is an expanding health problem with a great impact on morbidity and mortality, both in Egypt and worldwide. Recently, metformin and aspirin showed a potential anticancer effect on HCC, although the mechanism of this effect is not fully elucidated. OBJECTIVE: The current work aimed to investigate the possibility of targeting AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and β-catenin proteins through combined metformin/aspirin treatment in the HepG2 cell line, and to explore such molecular targets in Egyptian HCC patients...
November 1, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/29093327/chelerythrine-inhibits-human-hepatocellular-carcinoma-metastasis-in-vitro
#6
Yuanzhang Zhu, Yingyi Pan, Guibiao Zhang, Yingchun Wu, Weicai Zhong, Chunxiao Chu, Yun Qian, Guofu Zhu
Chelerythrine (CHE) is a type of benzophenanthridine alkaloid found in many herbs and is also the main alkaloid constituent of Toddalia asiatica (L.) Lam. It has been proven to have various activities including antitumor, antifungal, anti-inflammatory and anti-parasitic effects. We have previously demonstrated that CHE can inhibit proliferation and promote apoptosis in human hepatocellular carcinoma (HCC) cells. However, the effect of CHE on the metastasis of HCC and its related molecular mechanisms have yet to be validated...
October 31, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29074727/liver-reptin-ruvbl2-controls-glucose-and-lipid-metabolism-with-opposite-actions-on-mtorc1-and-mtorc2-signalling
#7
Joaquim Javary, Nathalie Allain-Courtois, Nicolas Saucisse, Pierre Costet, Capucine Heraud, Fadila Benhamed, Rémi Pierre, Corinne Bure, Nestor Pallares-Lupon, Marcio Do Cruzeiro, Catherine Postic, Daniela Cota, Pierre Dubus, Jean Rosenbaum, Samira Benhamouche-Trouillet
OBJECTIVE: The AAA+ ATPase Reptin is overexpressed in hepatocellular carcinoma and preclinical studies indicate that it could be a relevant therapeutic target. However, its physiological and pathophysiological roles in vivo remain unknown. This study aimed to determine the role of Reptin in mammalian adult liver. DESIGN AND RESULTS: We generated an inducible liver-specific Reptin knockout (Repin(LKO) ) mouse model. Following Reptin invalidation, mice displayed decreased body and fat mass, hypoglycaemia and hypolipidaemia...
October 26, 2017: Gut
https://www.readbyqxmd.com/read/29069736/a-novel-synthetic-derivative-of-quercetin-8-trifluoromethyl-3-5-7-3-4-o-pentamethyl-quercetin-inhibits-bladder-cancer-growth-by-targeting-the-ampk-mtor-signaling-pathway
#8
Ting Tao, Caimei He, Jun Deng, Yanjun Huang, Qiongli Su, Mei Peng, Meiling Yi, Kwame Oteng Darko, Hui Zou, Xiaoping Yang
Quercetin is a naturally existing compound and shows attractive anticancer properties for a variety of solid tumors including glioma, bladder cancer, hepatocellular carcinoma, breast cancer, hematological malignancies and prostate carcinoma. However, these anticancer properties have not been clinically approved due to unclear mechanistic information and its low bioactivity. In our previous study, we elucidated that quercetin activates AMPK pathway which is the major mechanism for its unique anticancer effect in bladder cancer...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29066806/phosphoinositide-specific-phospholipase-c%C3%AE-1-inhibition-induces-autophagy-in-human-colon-cancer-and-hepatocellular-carcinoma-cells
#9
Lianzhi Dai, Xiaolei Chen, Xiaohong Lu, Fen Wang, Yanyan Zhan, Gang Song, Tianhui Hu, Chun Xia, Bing Zhang
Phosphoinositide-specific phospholipase C (PLC) γ1 has been reported to be involved in cancer cell proliferation and metastasis. However, whether PLCγ1 modulates autophagy and the underlying mechanism remains unclear. Here, we investigated the relationship between PLCγ1 and autophagy in the human colon cancer cell line HCT116 and hepatocellular carcinoma cell line HepG2. The results indicated that PLCγ1 inhibition via lentivirus-mediated transduction with shRNA/PLCγ1 or transient transfection with pRK5-PLCγ1 (Y783A) vector increased LC3B-II levels and the number of autophagic vacuoles and decreased p62 levels...
October 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29050265/reactive-oxygen-species-dependent-phosphorylation-of-the-liver-kinase-b1-amp-activated-protein-kinase-acetyl-coa-carboxylase-signaling-is-critically-involved-in-apoptotic-effect-of-lambertianic-acid-in-hepatocellular-carcinoma-cells
#10
Arong Jeong, Ju-Ha Kim, Hyo-Jung Lee, Sung-Hoon Kim
Though lambertianic acid (LA) is reported to have hypolipidemic activity in liver, its underlying anticancer mechanism is poorly understood so far. Thus, in the present study, apoptotic mechanism of LA was elucidated in HepG2 and SK-Hep1 hepatocellular carcinoma (HCC) cells. Here LA increased cytotoxicity, sub-G1 population and Annexin V/PI positive cells in two HCC cells. Also, LA cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP), activated phosphorylation of liver kinase B1 (LKB1)/AMP activated protein kinase (AMPK)/ acetyl-CoA carboxylase (ACC) pathway and also suppressed antiapoptotic proteins such as phosphorylation of Akt/ mammalian target of rapamycin (mTOR) and the expression of B cell lymphoma-2 (Bcl-2)/ B-cell lymphoma-extra large (Bcl-xL) and cyclooxygenase-2 (COX-2) in two HCC cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048654/telmisartan-inhibits-hepatocellular-carcinoma-cell-proliferation-in-vitro-by-inducing-cell-cycle-arrest
#11
Kyoko Oura, Tomoko Tadokoro, Shintaro Fujihara, Asahiro Morishita, Taiga Chiyo, Eri Samukawa, Yoshimi Yamana, Koji Fujita, Teppei Sakamoto, Takako Nomura, Hirohito Yoneyama, Hideki Kobara, Hirohito Mori, Hisakazu Iwama, Keiichi Okano, Yasuyuki Suzuki, Tsutomu Masaki
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third leading cause of cancer-related death. Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB) that might inhibit cancer cell proliferation, but the mechanisms through which telmisartan affects various cancers remain unknown. The aim of the present study was to evaluate the effects of telmisartan on human HCC and to assess the expression of microRNAs (miRNAs). We studied the effects of telmisartan on HCC cells using the HLF, HLE, HepG2, HuH-7 and PLC/PRF/5 cell lines...
September 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29042961/the-long-non-coding-rna-ak023948-enhances-tumor-progression-in-hepatocellular-carcinoma
#12
Bailiang Ye, Bingren Hu, Zhihai Zheng, Ru Zheng, Yixiong Shi
The long non-coding RNAs (lncRNAs) have been demonstrated to play pivotal roles in a broad range of processes including tumor biology. However, the exact contributions of lncRNAs to hepatocellular carcinoma (HCC) remain poorly defined. In current study, we have unraveled a novel function of AK023948 in HCC. We found that AK023948 was substantially upregulated in tumor tissues. Meanwhile, higher AK023948 expression correlated with poor survival. Upregulation of AK023948 expression can promote HepG2 and Hep3B proliferation and invasion in in vitro experiments...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29038587/cell-surface-major-vault-protein-promotes-cancer-progression-through-harboring-mesenchymal-and-intermediate-circulating-tumor-cells-in-hepatocellular-carcinomas
#13
Hyun Min Lee, Jae Won Joh, Se-Ri Seo, Won-Tae Kim, Min Kyu Kim, Hong Seo Choi, So Young Kim, Young-Joo Jang, Dong Hyun Sinn, Gyu Seong Choi, Jong Man Kim, Choon Hyuck David Kwon, Hee Jin Chang, Dae Shick Kim, Chun Jeih Ryu
Circulating tumor cells (CTCs) play a major role in the metastasis and recurrence of hepatocellular carcinoma (HCC). Here, we found that major vault protein (MVP) is expressed on the surface of HCC cells and further induced under stressful environments. MVP knockdown reduces cell proliferation and induces apoptosis in HCC cells. Treatment of HCC cells with anti-MVP antibody (α-MVP) recognizing cell-surface MVP (csMVP) inhibits cell proliferation, migration, and invasion. csMVP-positive HCC cells have a higher clonogenic survival than csMVP-negative HCC cells, and treatment of HCC cells with α-MVP inhibits clonogenic survival, suggesting that csMVP contributes to HCC cell survival, migration, and invasion...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29032337/mir-758-3p-suppresses-proliferation-migration-and-invasion-of-hepatocellular-carcinoma-cells-via-targeting-mdm2-and-mtor
#14
Dan Jiang, William Cho, Zhenhao Li, Xiangrong Xu, Yuliang Qu, Zhongjia Jiang, Le Guo, Guangxian Xu
Hepatocelluar carcinoma (HCC) is one of the most frequently diagnosed cancers worldwide and among the leading causes of cancer-related death. Although deregulation of microRNAs has been frequently described in HCC, imperfection is known about the precise molecular mechanisms by which microRNAs modulate the process of tumorogenesis and behavior of cancer cells. In this study, we demonstrated that miR-758-3p could suppress cell proliferation, migration and invasion in hepatocellular carcinoma cells. We screened and identified two novel miR-758-3p targets, MDM2 and mTOR...
October 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29029500/edg2-enhanced-the-progression-of-hepatocellular-carcinoma-by-lpa-pi3k-akt-mtor-signaling
#15
Meng Xu, Zhikui Liu, Cong Wang, Bowen Yao, Xin Zheng
HCC is the leading type of the malignant liver tumors with the unsatisfied prognosis. Liver resection has been considered as the predominant curative therapy, however, the post-surgical prognostic evaluation remains an urgent problem and the mechanism of HCC metastases has not been understood completely. EDG2 has been found to accelerate tumor progression through mediating different cell pathways, however, it remains unclear about the role of EDG2 on hepatocarcinogenesis. Here, EDG2 expression was found increased notably in HCC tissues by immunohistochemistry compared with adjacent liver tissues and comparison of survival curves revealed that EDG2 upregulation in HCC tissues was associated with the worse prognosis after liver resection...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29027712/upregulation-of-ube2q1-via-gene-copy-number-gain-in-hepatocellular-carcinoma-promotes-cancer-progression-through-%C3%AE-catenin-egfr-pi3k-akt-mtor-signaling-pathway
#16
Bin Zhang, Chao Deng, Lei Wang, Fan Zhou, Shu Zhang, Wei Kang, Ping Zhan, Juan Chen, Shanshan Shen, Huimin Guo, Ming Zhang, Yi Wang, Feng Zhang, Wei Zhang, Jiangqiang Xiao, Bo Kong, Helmut Friess, Yuzheng Zhuge, Hongli Yan, Xiaoping Zou
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and represents a highly malignant tumor with a poor prognosis. Therapeutic modalities for HCC are limited and generally ineffective. UBE2Q1 is a putative E2 ubiquitin conjugating enzyme, and has been shown to be overexpressed in various types of cancers including HCC. How UBE2Q1 contributes to hepatocarcinogenesis remains unknown. Here, we show that UBE2Q1 is up-regulated in HCC cell lines and in a subset of human HCC tissues. Up-regulation of UBE2Q1 in primary HCC tumors was significantly correlated with shorter overall survival and disease-free survival...
October 13, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28978011/aldose-reductase-interacts-with-akt1-to-augment-hepatic-akt-mtor-signaling-and-promote-hepatocarcinogenesis
#17
Jia-Xing Zhao, Ya-Wei Yuan, Cheng-Fu Cai, Dong-Yan Shen, Mao-Li Chen, Feng Ye, Yan-Jun Mi, Qi-Cong Luo, Wang-Yu Cai, Wei Zhang, Ying Long, Yong Zeng, Guo-Dong Ye, Shu-Yu Yang
Marked up-regulation of aldose reductase (AR) is reportedly associated with the development of hepatocellular carcinoma (HCC). We investigated how aberrantly overexpressed AR might promote oncogenic transformation in liver cells and tissues. We found that overexpressed AR interacted with the kinase domain of AKT1 to increase AKT/mTOR signaling. In both cultured liver cancer cells and liver tissues in DEN-induced transgenic HCC model mice, we observed that AR overexpression-induced AKT/mTOR signaling tended to enhance lactate formation and hepatic inflammation to enhance hepatocarcinogenesis...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974556/lycorine-promotes-autophagy-and-apoptosis-via-tcrp1-akt-mtor-axis-inactivation-in-human-hepatocellular-carcinoma
#18
Haiyang Yu, Yuling Qiu, Xu Pang, Jian Li, Song Wu, Shuangshuang Yin, Lifeng Han, Yi Zhang, Chengyun Jin, Xiumei Gao, Wenwei Hu, Tao Wang
Lycorine is a multi-functional bioactive compound, and it possesses potential anti-cancer activities. However, little is known about the underlying mechanism. In this research we have found that lycorine significantly induces the apoptotic and autophagic capacities of hepatocellular carcinoma (HCC) cells in vitro and in vivo. Treatment with specific autophagy inhibitor (3-methyladenine/Bafilomycin A1) or knockdown of LC-3B/Atg5 by siRNA drastically enhances the apoptotic cell death effect by facilitating the switch from autophagy to apoptosis...
September 28, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28968944/anti-hepatocarcinoma-effect-of-cordycepin-against-ndea-induced-hepatocellular-carcinomas-via-the-pi3k-akt-mtor-and-nrf2-ho-1-nf-%C3%AE%C2%BAb-pathway-in-mice
#19
Yongming Zeng, Shuyi Lian, Danfeng Li, Xiaosheng Lin, Bozan Chen, Hongfa Wei, Tian Yang
The purpose of the present study was to evaluate the effects of cordycepin (CA) on N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinomas (HCC) and explore its potential mechanisms. Mice were randomly assigned to four groups: control group, NDEA group, NDEA+CA (20mg/kg) group, NDEA+CA (40mg/kg) group. The animal of each group were given NDEA (100ppm) in drinking water. One hour later, CA, which was dissolved in PBS, were intragastrically administered for continuous seven days. The results showed that CA reduced the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in liver and serum...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28954551/heat-stress-induced-ligand-independent-met-and-egfr-signaling-in-hepatocellular-carcinoma
#20
Scott M Thompson, Danielle E Jondal, Kim A Butters, Bruce E Knudsen, Jill L Anderson, Matthew P Stokes, Xiaoying Jia, Joseph P Grande, Lewis R Roberts, Matthew R Callstrom, David A Woodrum
PURPOSE: The aims of the present study were two-fold: first, to test the hypothesis that heat stress induces MET and EGFR signaling in hepatocellular carcinoma (HCC) cells and inhibition of this signaling decreases HCC clonogenic survival; and second, to identify signaling pathways associated with heat-stress induced MET signaling. MATERIALS AND METHODS: MET(+) and EGFR(+) HCC cells were pre-treated with inhibitors to MET, EGFR, PI3K/mTOR or vehicle and subjected to heat stress or control ± HGF or EGF growth factors and assessed by colony formation assay, Western blotting and/or quantitative mass spectrometry...
September 27, 2017: International Journal of Hyperthermia
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