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Hepatocellular carcinoma mtor

Shoji Yamada, Yoko Takashina, Mitsuhiro Watanabe, Ryogo Nagamine, Yoshimasa Saito, Nobuhiko Kamada, Hidetsugu Saito
Gut microbiota plays a significant role in the development of hepatocellular carcinoma (HCC) in non-alcoholic steatohepatitis (NASH). However, understanding of the precise mechanism of this process remains incomplete. A new class steatohepatitis-inducing high-fat diet (HFD), namely STHD-01, can promote the development of HCC without the administration of chemical carcinogens. Using this diet, we comprehensively analyzed changes in the gut microbiota and its metabolic functions during the development of HCC in NASH...
February 9, 2018: Oncotarget
Boris Rodenak-Kladniew, Agustina Castro, Peter Stärkel, Christine De Saeger, Margarita García de Bravo, Rosana Crespo
AIMS: Linalool is a plant-derived monoterpene with anticancer activity, however its mechanisms of action remain poorly understood. The aim of this work was to elucidate the anticancer mechanisms of action of linalool in hepatocellular carcinoma (HCC) HepG2 cells. MAIN METHODS: Cell viability and proliferation were determined by WST-1 assay and BrdU incorporation, respectively. Cell cycle analysis was assessed through flow cytometry (FC) and western blot (WB). Apoptosis was determined by caspase-3 activity, TUNEL assay and WB...
March 3, 2018: Life Sciences
Laura Berliocchi, Carlotta Chiappini, Annagrazia Adornetto, Debora Gentile, Silvia Cerri, Rossella Russo, Giacinto Bagetta, Maria Tiziana Corasaniti
BACKGROUND: d-Limonene is a natural monoterpene abundant in Citrus essential oils. It is endowed with several biological activities, including inhibition of carcinogenesis and promotion of tumour regression. Recently, d-limonene has been shown to modulate autophagic markers in vitro at concentrations found in vivo, in clinical pharmacokinetic studies. Autophagy is an intracellular catabolic process serving as both an adaptive metabolic response and a quality control mechanism. Because autophagy defects have been linked to a wide range of human pathologies, including neurodegeneration and cancer, there is a need for new pharmacological tools to control deregulated autophagy...
February 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Chloé Sauzay, Christophe Louandre, Sandra Bodeau, Frédéric Anglade, Corinne Godin, Zuzana Saidak, Jean-Xavier Fontaine, Cédric Usureau, Nathalie Martin, Roland Molinie, Julie Pascal, François Mesnard, Olivier Pluquet, Antoine Galmiche
Sorafenib is the first line treatment for advanced hepatocellular carcinoma (HCC). We explored its impact on the proteostasis of cancer cells, i.e. the processes that regulate the synthesis, maturation and turn-over of cellular proteins. We observed that sorafenib inhibits the production of the tumour marker alpha-foetoprotein (AFP) in two different HCC cell lines, an effect that correlated with a radical inhibition of protein biosynthesis. This effect was observed at clinically relevant concentrations of sorafenib and was not related to the effect of sorafenib on the transport of amino acids across the plasma membrane or the induction of the unfolded protein response (UPR)...
February 2, 2018: Oncotarget
Hui Hua, Yu Zhu, Yu-He Song
BACKGROUND: Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related mortality with poor prognosis and treatment. More effective strategies should be studied in HCC. METHODS: After treated with ruscogenin, the cell proliferation was assessed by CCK-8 method. Cell migration and invasion were estimated using wound healing and transwell assays. Pathological changes of lung tissue were observed by HE staining and IHC methods. MMP-2, MMP-9, uPA, VEGF and HIF-1α levels were measured using ELISA, RT-qPCR and WB tests...
February 22, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jun Li, Peng-Wen Wu, Yuan Zhou, Bo Dai, Peng-Fei Zhang, Yu-Hen Zhang, Yang Liu, Xiao-Lei Shi
The receptor for advanced glycation end products (Rage) is involved in the development of various tumors and acts as an oncogenic protein. Rage is overexpressed in tumors including hepatocellular carcinoma (HCC). However, the molecular mechanism of Rage in HCC progression and sorafenib resistance remains unclear. In this study, enhanced Rage expression is highly associated proliferation and contributes to sorafenib resistance. Rage deficiency contributed to autophagy induction through activating AMPK/mTOR signaling pathway, which is important for sorafenib response...
February 14, 2018: Cell Death & Disease
Na Zhang, Xiaojia Liu, Lu Liu, Zhesong Deng, Qingxuan Zeng, Weiqiang Pang, Yang Liu, Danqing Song, Hongbin Deng
Glycogen synthase kinase-3β (GSK-3β) is a ubiquitously expressed serine/threonine kinase involved in a variety of functions ranging from the control of glycogen metabolism to transcriptional regulation. We recently demonstrated that GSK-3β inhibition triggered ASK1-JNK-dependent apoptosis in human hepatocellular carcinoma (HCC) cells. However, the comprehensive picture of downstream GSK-3β-regulated pathways/functions remains elusive. In this study, we showed that GSK-3β was aberrantly activated in HCC...
February 14, 2018: Cell Death & Disease
Venkat Bhat, Sujitha Srinathan, Elisa Pasini, Marc Angeli, Emily Chen, Cristina Baciu, Mamatha Bhat
AIM: To identify the key epigenetically modulated genes and pathways in HCC by performing an integrative meta-analysis of all major, well-annotated and publicly available methylation datasets using tools of network analysis. METHODS: PubMed and Gene Expression Omnibus were searched for genome-wide DNA methylation datasets. Patient clinical and demographic characteristics were obtained. DNA methylation data were integrated using the Ingenuity Pathway Analysis, a software package for visualizing and analyzing biological networks...
January 27, 2018: World Journal of Hepatology
José A Del Campo, Marta García-Valdecasas, Antonio Gil-Gómez, Ángela Rojas, Paloma Gallego, Javier Ampuero, Rocío Gallego-Durán, Helena Pastor, Lourdes Grande, Francisco J Padillo, Jordi Muntané, Manuel Romero-Gómez
Hepatitis C virus (HCV) infection has been related to increased risk of development of hepatocellular carcinoma (HCC) while metformin (M) and statins treatment seemed to protect against HCC development. In this work, we aim to identify the mechanisms by which metformin and simvastatin (S) could protect from liver cancer. Huh7.5 cells were infected with HCV particles and treated with M+S. Human primary hepatocytes were treated with M+S. Treatment with both drugs inhibited Huh7.5 cell growth and HCV infection...
2018: PloS One
Chao-Yue Sun, Ying Zhu, Xiao-Feng Li, Li-Peng Tang, Zu-Qing Su, Xie-Qi Wang, Cai-Yun Li, Hong-Mei Yang, Guang-Juan Zheng, Bing Feng
There is an urgent need for effective molecular therapies for hepatocellular carcinoma (HCC), the third-leading cause of cancer-related deaths worldwide. Norcantharidin (NCTD), a demethylated derivative of cantharidin, reportedly exhibits anticancer activity against various types of tumors, including HCC, though the mechanisms involved remain largely unknown. Here, we report that NCTD reduces viability of human MHCC-97H (97H) and HepG2 HCC cells, and induces cell death by triggering high levels of autophagy...
December 29, 2017: Oncotarget
Dizhong Chen, Chang Kai Soh, Wei Huang Goh, Haishan Wang
Class I histone deacetylases (HDACs) are highly expressed and/or upregulated in hepatocellular carcinoma (HCC) and are associated with aggressiveness, spread, and increased mortality of HCC. Activation of phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway was involved in the development of HCC and acquired resistance to sorafenib. A series of purine or 5H-pyrrolo[3,2-d]pyrimidine based hydroxamates were designed and developed as multi-target drugs to modulate both HDACs and the PI3K/Akt/mTOR pathway...
January 23, 2018: Journal of Medicinal Chemistry
Kai Dai, Yabing Huang, Zubing Chen, Xiaomei Sun, Lihua Yang, Yingan Jiang
Natural killer cell (NK cell)-based immunotherapy is a promising therapeutic strategy for hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the regulation of NK cell function in the tumor sites are not completely elucidated. In this study, we identified the enhanced expression of kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2) in intratumoral NK cells in a mouse HCC implantation model as a negative regulator of NK cells. To investigate this interaction,, we used a Tet-on inducible expression system to control Kbtbd2 expression in an immortalized mouse NK cell line KIL C...
January 13, 2018: European Journal of Immunology
Guangning Zhang, Dongyuan Li, Hao Chen, Junchen Zhang, Xingyi Jin
Glioblastoma is a common primary brain tumor with aggressive malignancy, which results in poor outcomes, short survival time and high mortality. Vitexin, an active ingredient from natural products, has been reported to inhibit cell growth and induce cell apoptosis in various cancer cell lines including hepatocellular carcinoma, oral and esophageal cancer. To the best of the authors knowledge, the present study was the first to investigate anticancer effects of vitexin on human glioblastoma cells and potential underlying mechanisms...
January 8, 2018: Molecular Medicine Reports
Richard Jennemann, Giuseppina Federico, Daniel Mathow, Mariona Rabionet, Francesca Rampoldi, Zoran V Popovic, Martina Volz, Thomas Hielscher, Roger Sandhoff, Hermann-Josef Gröne
Hepatocellular carcinoma (HCC) is one of the most frequent cancers. In vitro studies suggest that growth and response to therapy of human carcinomas may depend on glycosphingolipid (GSL) expression. Glucosylceramide synthase (GCS), encoded by the gene Ugcg, is the basic enzyme required for the synthesis of GSLs. Gene array analysis implied that Ugcg is significantly overexpressed in human HCC as compared to non-tumorous liver tissue. Therefore we have investigated whether tumor - genesis and - growth is altered in the absence of GSLs...
December 12, 2017: Oncotarget
Daniela Pollutri, Clarissa Patrizi, Sara Marinelli, Catia Giovannini, Elena Trombetta, Ferdinando A Giannone, Maurizio Baldassarre, Santina Quarta, Y P Vandewynckel, A Vandierendonck, H Van Vlierberghe, Laura Porretti, Massimo Negrini, Luigi Bolondi, Laura Gramantieri, Francesca Fornari
Hepatocellular carcinoma (HCC) represents the second cause of cancer-related mortality worldwide and is associated with poor prognosis, especially in patients not amenable for curative treatments. The multi-kinase inhibitor sorafenib represents the first-line treatment option for advanced HCC; nevertheless, its effectiveness is limited due to tumor heterogeneity as well as innate or acquired drug resistance, raising the need for new therapeutic strategies. MicroRNAs (miRNAs) involvement in treatment response as well as their safety and efficacy in preclinical models and clinical trials have been widely documented in the oncologic field, including HCC...
January 5, 2018: Cell Death & Disease
Zhong Xu, Junjie Hu, Hui Cao, Maria G Pilo, Antonio Cigliano, Zixuan Shao, Meng Xu, Silvia Ribback, Frank Dombrowski, Diego F Calvisi, Xin Chen
Hepatocellular carcinoma (HCC) is a deadly malignancy with limited treatment options. Activation of the AKT/mTOR cascade is one of the most frequent events along hepatocarcinogenesis. mTOR is a serine/threonine kinase and presents in two distinct complexes: mTORC1 and mTORC2. While mTORC1 has been extensively studied in HCC, the functional contribution of mTORC2 during hepatocarcinogenesis has not been well characterized, especially in vivo. Pten expression is one of the major mechanisms leading to the aberrant activation of the AKT/mTOR signaling...
January 5, 2018: Experimental & Molecular Medicine
Yu Zhang, Kaiqiang Li, Youmin Ying, Bingyu Chen, Ke Hao, Boxu Chen, Yu Zheng, Jianxin Lyu, Xiangming Tong, Xiaopan Chen, Ying Wang, Zhajun Zhan, Wei Zhang, Zhen Wang
Marsdenia tenacissimae extraction (MTE), a traditional herbal medicine, has exhibited anti-tumor effects on a variety of cancers. However, its effectiveness and the mechanism of action in Hepatocellular carcinoma (HCC) has not been fully understood. In the present study, we demonstrate that C21 steroid-enriched fraction from MTE, which contains five main C21 steroids (FR5) exhibits obvious pharmacological activities on HCC cells in vitro and in vivo. FR5 induces apoptosis and inhibits proliferation and migration of HepG2 and Bel7402 cells in a dose and time dependent manner...
December 15, 2017: Oncotarget
Kenta Yokoi, Akira Kobayashi, Hiroaki Motoyama, Masato Kitazawa, Akira Shimizu, Tsuyoshi Notake, Takahide Yokoyama, Tomio Matsumura, Michiko Takeoka, Shin-Ichi Miyagawa
Cholangiocarcinoma (CCC) is a strongly aggressive malignancy for which surgical resection is the only potential curative therapy. Sorafenib, a multikinase inhibitor of the RAF/MEK/ERK pathway, is a molecular-targeted drug that is approved for hepatocellular carcinoma (HCC) but not for CCC. The differences in signaling pathway characteristics under sorafenib treatment between HCC (HLF, Huh7, PLC/PRF/5) and CCC (RBE, YSCCC, Huh28) cell lines were therefore investigated using cell proliferation, western blotting, and apoptosis analyses...
February 2018: Oncology Reports
Catia Giovannini, Francesca Fornari, Rossella Dallo, Martina Gagliardi, Elisa Nipoti, Francesco Vasuri, Camelia Alexandra Coadă, Matteo Ravaioli, Luigi Bolondi, Laura Gramantieri
Hepatocellular carcinoma (HCC) represents the second cause of cancer-related mortality worldwide and is associated with poor prognosis, due to a high recurrence rate after curative treatments and a drug resistance phenotype. In this scenario, the identification of innovative and effective therapeutic strategies is an unmet clinical need. The safety and efficacy of microRNA (miRNA) mediated approaches in preclinical models and clinical trials have been widely described in cancer. MicroRNA-199a downregulation is a common feature of HCC where its reduced expression contributes to mTOR and c-Met pathways activation...
December 14, 2017: Acta Histochemica
Minjing Li, Changzhu Jin, Maolei Xu, Ling Zhou, Defang Li, Yancun Yin
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the cancer types with poor prognosis. To effectively treat HCC, new molecular targets and therapeutic approaches must be identified. 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate (IMP) cyclohydrolase (ATIC), a bifunctional protein enzyme, catalyzes the last two steps of the de novo purine biosynthetic pathway. Whether ATIC contributes to cancer development remains unclear. METHODS: ATIC mRNA levels in different types of human HCC samples or normal tissues were determined from Gene Expression across Normal and Tumor tissue (GENT) database...
December 16, 2017: Cell Communication and Signaling: CCS
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