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For: Liang C, Jung JU. Autophagy genes as tumor suppressors. Curr Opin Cell Biol 2010;22:226-33. [PMID: 19945837 DOI: 10.1016/j.ceb.2009.11.003] [Citation(s) in RCA: 70] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2009] [Accepted: 11/05/2009] [Indexed: 12/13/2022]

For:	Liang C, Jung JU. Autophagy genes as tumor suppressors. Curr Opin Cell Biol 2010;22:226-33. [PMID: 19945837 DOI: 10.1016/j.ceb.2009.11.003] [Citation(s) in RCA: 70] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2009] [Accepted: 11/05/2009] [Indexed: 12/13/2022]

Number

Cited by Other Article(s)

Taha SR, Karimi M, Mahdavi B, Yousefi Tehrani M, Bemani A, Kabirian S, Mohammadi J, Jabbari S, Hushmand M, Mokhtar A, Pourhanifeh MH. Crosstalk between non-coding RNAs and programmed cell death in colorectal cancer: implications for targeted therapy. Epigenetics Chromatin 2025;18:3. [PMID: 39810224 PMCID: PMC11734566 DOI: 10.1186/s13072-024-00560-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 11/13/2024] [Indexed: 01/16/2025] Open

Guo J, Chen Q, Han S, Wang T, Xia K, Yu B, Qiu T, Zhou J. Construction of an autophagy-related genes risk model as predicting prognosis: BAG1 suppresses growth of clear cell renal cell carcinoma. Int Immunopharmacol 2024;140:112737. [PMID: 39128415 DOI: 10.1016/j.intimp.2024.112737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 07/17/2024] [Accepted: 07/18/2024] [Indexed: 08/13/2024]

Abstract

BACKGROUND

The incidence of clear cell renal cell carcinoma (ccRCC) is increasing annually. While the cure rate and prognosis of early ccRCC are promising, the 5-year survival rate of patients with metastatic ccRCC is below 12%. Autophagy disfunction is closely related to infection, cancer, neurodegeneration and aging. Nevertheless, there has been limited exploration of the association between autophagy and ccRCC through bioinformatics analysis.

METHODS

A novel risk model of autophagy-related genes (ARGs) was constructed to predict the prognosis of patients with ccRCC and guide the individualized treatment to some extent. Relevant data samples were obtained from the TCGA database, and ccRCC-related ARGs were identified by Pearson correlation analysis, leading to the establishment of a risk model covering 10 ccRCC-related ARGs. Many indicators were used to assess the accuracy of the risk model.

RESULTS

Receiver operating characteristic (ROC) curve analysis showed that the risk model had high accuracy, indicating that the risk model could predict the prognosis of ccRCC patients. Moreover, the findings revealed significant differences about immune and metabolic features in low- and high-risk groups. The study also found that BAG1 within the risk model was closely related to the prognosis of ccRCC and an independent risk factor. In vitro and in vivo experiments validated for the first time that BAG1 could suppress the proliferation, migration, and invasion of ccRCC.

CONCLUSION

The construction of ARGs risk model, can well predict the prognosis of ccRCC patients, and provide guidance for individual therapy to patients. It was also found that BAG1 has significant prognostic value for ccRCC patients and acts as a tumor suppressor gene in ccRCC. These findings have crucial implications for the prognosis and treatment of ccRCC patients.

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Dong Y, He Y, Geng Y, Wei M, Zhou X, Lian J, Hallajzadeh J. Autophagy-related lncRNAs and exosomal lncRNAs in colorectal cancer: focusing on lncRNA-targeted strategies. Cancer Cell Int 2024;24:328. [PMID: 39342235 PMCID: PMC11439232 DOI: 10.1186/s12935-024-03503-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 09/06/2024] [Indexed: 10/01/2024] Open

Hsueh TC, Chen PH, Hong JR. ISKNV Triggers AMPK/mTOR-Mediated Autophagy Signaling through Oxidative Stress, Inducing Antioxidant Enzyme Expression and Enhancing Viral Replication in GF-1 Cells. Viruses 2024;16:914. [PMID: 38932206 PMCID: PMC11209599 DOI: 10.3390/v16060914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 05/25/2024] [Accepted: 06/01/2024] [Indexed: 06/28/2024] Open

Abstract

Infectious spleen and kidney necrosis virus (ISKNV) infections can induce the process of host cellular autophagy but have rarely been identified within the molecular autophagy signaling pathway. In the present study, we demonstrated that ISKNV induces ROS-mediated oxidative stress signals for the induction of 5'AMP-activated protein kinase/mechanistic target of rapamycin kinase (AMPK/mTOR)-mediated autophagy and upregulation of host antioxidant enzymes in fish GF-1 cells. We also examined ISKNV-induced oxidative stress, finding that reactive oxidative species (ROS) increased by 1.5-fold and 2.5-fold from day 2 to day 3, respectively, as assessed by the H2DCFDA assay for tracing hydrogen peroxide (H2O2), which was blocked by NAC treatment in fish GF-1 cells. Furthermore, ISKNV infection was shown to trigger oxidative stress/Nrf2 signaling from day 1 to day 3; this event was then correlated with the upregulation of antioxidant enzymes such as Cu/ZnSOD and MnSOD and was blocked by the antioxidant NAC. Using an MDC assay, TEM analysis and autophagy marker LC3-II/I ratio, we found that ROS stress can regulate autophagosome formation within the induction of autophagy, which was inhibited by NAC treatment in GF-1 cells. Through signal analysis, we found that AMPK/mTOR flux was modulated through inhibition of mTOR and activation of AMPK, indicating phosphorylation levels of mTOR Ser 2448 and AMPK Thr 172 from day 1 to day 3; however, this process was reversed by NAC treatment, which also caused a reduction in virus titer (TCID50%) of up to 1000 times by day 3 in GF-1 cells. Thus, ISKNV-induced oxidative stress signaling is blocked by antioxidant NAC, which can also either suppress mTOR/AMPK autophagic signals or reduce viral replication. These findings may provide the basis for the creation of DNA control and treatment strategies.

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Tiwari M, Srivastava P, Abbas S, Jegatheesan J, Ranjan A, Sharma S, Maurya VP, Saxena AK, Sharma LK. Emerging Role of Autophagy in Governing Cellular Dormancy, Metabolic Functions, and Therapeutic Responses of Cancer Stem Cells. Cells 2024;13:447. [PMID: 38474411 PMCID: PMC10930960 DOI: 10.3390/cells13050447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 02/28/2024] [Accepted: 02/29/2024] [Indexed: 03/14/2024] Open

Abstract

Tumors are composed of heterogeneous populations of dysregulated cells that grow in specialized niches that support their growth and maintain their properties. Tumor heterogeneity and metastasis are among the major hindrances that exist while treating cancer patients, leading to poor clinical outcomes. Although the factors that determine tumor complexity remain largely unknown, several genotypic and phenotypic changes, including DNA mutations and metabolic reprograming provide cancer cells with a survival advantage over host cells and resistance to therapeutics. Furthermore, the presence of a specific population of cells within the tumor mass, commonly known as cancer stem cells (CSCs), is thought to initiate tumor formation, maintenance, resistance, and recurrence. Therefore, these CSCs have been investigated in detail recently as potential targets to treat cancer and prevent recurrence. Understanding the molecular mechanisms involved in CSC proliferation, self-renewal, and dormancy may provide important clues for developing effective therapeutic strategies. Autophagy, a catabolic process, has long been recognized to regulate various physiological and pathological processes. In addition to regulating cancer cells, recent studies have identified a critical role for autophagy in regulating CSC functions. Autophagy is activated under various adverse conditions and promotes cellular maintenance, survival, and even cell death. Thus, it is intriguing to address whether autophagy promotes or inhibits CSC functions and whether autophagy modulation can be used to regulate CSC functions, either alone or in combination. This review describes the roles of autophagy in the regulation of metabolic functions, proliferation and quiescence of CSCs, and its role during therapeutic stress. The review further highlights the autophagy-associated pathways that could be used to regulate CSCs. Overall, the present review will help to rationalize various translational approaches that involve autophagy-mediated modulation of CSCs in controlling cancer progression, metastasis, and recurrence.

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Tanaka M, Sugimoto K, Akasaka H, Yoshida S, Takahashi T, Fujimoto T, Xie K, Yasunobe Y, Yamamoto K, Hirabayashi T, Nakanishi R, Fujino H, Rakugi H. Effects of interleukin-15 on autophagy regulation in the skeletal muscle of mice. Am J Physiol Endocrinol Metab 2024;326:E326-E340. [PMID: 38294696 DOI: 10.1152/ajpendo.00311.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 01/19/2024] [Accepted: 01/19/2024] [Indexed: 02/01/2024]

Abstract

This study aimed to evaluate the role of skeletal muscle-derived interleukin (IL)-15 in the regulation of skeletal muscle autophagy using IL-15 knockout (KO) and transgenic (TG) mice. Male C57BL/6 wild-type (WT), IL-15 KO, and IL-15 TG mice were used in this study. Changes in muscle mass, forelimb grip strength, succinate dehydrogenase (SDH) activity, gene and protein expression levels of major regulators and indicators of autophagy, comprehensive gene expression, and DNA methylation in the gastrocnemius muscle were analyzed. Enrichment pathway analyses revealed that the pathology of IL-15 gene deficiency was related to the autophagosome pathway. Moreover, although IL-15 KO mice maintained gastrocnemius muscle mass, they exhibited a decrease in autophagy induction. IL-15 TG mice exhibited a decrease in gastrocnemius muscle mass and an increase in forelimb grip strength and SDH activity in skeletal muscle. In the gastrocnemius muscle, the ratio of phosphorylated adenosine monophosphate-activated protein kinase α (AMPKα) to total AMPKα and unc-51-like autophagy activating kinase 1 and Beclin1 protein expression were higher in the IL-15 TG group than in the WT group. IL-15 gene deficiency induces a decrease in autophagy induction. In contrast, IL-15 overexpression could improve muscle quality by activating autophagy induction while decreasing muscle mass. The regulation of IL-15 in autophagy in skeletal muscles may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.NEW & NOTEWORTHY IL-15 gene deficiency can decrease autophagy induction. However, although IL-15 overexpression induced a decrease in muscle mass, it led to an improvement in muscle quality. Based on these results, understanding the role of IL-15 in regulating autophagy pathways within skeletal muscle may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.

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Dalle Carbonare L, Minoia A, Vareschi A, Piritore FC, Zouari S, Gandini A, Meneghel M, Elia R, Lorenzi P, Antoniazzi F, Pessoa J, Zipeto D, Romanelli MG, Guardavaccaro D, Valenti MT. Exploring the Interplay of RUNX2 and CXCR4 in Melanoma Progression. Cells 2024;13:408. [PMID: 38474372 PMCID: PMC10930675 DOI: 10.3390/cells13050408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 02/20/2024] [Accepted: 02/25/2024] [Indexed: 03/14/2024] Open

Affiliation(s)

Luca Dalle Carbonare Department of Engineering for Innovative Medicine, University of Verona, 37134 Verona, Italy; (L.D.C.); (A.M.); (A.V.); (S.Z.)
Arianna Minoia Department of Engineering for Innovative Medicine, University of Verona, 37134 Verona, Italy; (L.D.C.); (A.M.); (A.V.); (S.Z.)
Anna Vareschi Department of Engineering for Innovative Medicine, University of Verona, 37134 Verona, Italy; (L.D.C.); (A.M.); (A.V.); (S.Z.)
Francesca Cristiana Piritore Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy; (F.C.P.); (M.M.); (P.L.); (D.Z.); (M.G.R.)
Sharazed Zouari Department of Engineering for Innovative Medicine, University of Verona, 37134 Verona, Italy; (L.D.C.); (A.M.); (A.V.); (S.Z.)
Alberto Gandini Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37134 Verona, Italy; (A.G.); (F.A.)
Mirko Meneghel Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy; (F.C.P.); (M.M.); (P.L.); (D.Z.); (M.G.R.)
Rossella Elia Department of Medicine, University of Verona, 37134 Verona, Italy;
Pamela Lorenzi Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy; (F.C.P.); (M.M.); (P.L.); (D.Z.); (M.G.R.)
Franco Antoniazzi Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37134 Verona, Italy; (A.G.); (F.A.)
João Pessoa Department of Medical Sciences and Institute of Biomedicine—iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal;
Donato Zipeto Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy; (F.C.P.); (M.M.); (P.L.); (D.Z.); (M.G.R.)
Maria Grazia Romanelli Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy; (F.C.P.); (M.M.); (P.L.); (D.Z.); (M.G.R.)
Daniele Guardavaccaro Department of Biotechnology, University of Verona, 37134 Verona, Italy;
Maria Teresa Valenti Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy; (F.C.P.); (M.M.); (P.L.); (D.Z.); (M.G.R.)

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Xu JY, Fan JX, Hu M, Zeng J. Microorganism-regulated autophagy in gastrointestinal cancer. PeerJ 2023;11:e16130. [PMID: 37786582 PMCID: PMC10541808 DOI: 10.7717/peerj.16130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 08/28/2023] [Indexed: 10/04/2023] Open

Clavero E, Sanchez-Maldonado JM, Macauda A, Ter Horst R, Sampaio-Marques B, Jurczyszyn A, Clay-Gilmour A, Stein A, Hildebrandt MAT, Weinhold N, Buda G, García-Sanz R, Tomczak W, Vogel U, Jerez A, Zawirska D, Wątek M, Hofmann JN, Landi S, Spinelli JJ, Butrym A, Kumar A, Martínez-López J, Galimberti S, Sarasquete ME, Subocz E, Iskierka-Jażdżewska E, Giles GG, Rybicka-Ramos M, Kruszewski M, Abildgaard N, Verdejo FG, Sánchez Rovira P, da Silva Filho MI, Kadar K, Razny M, Cozen W, Pelosini M, Jurado M, Bhatti P, Dudzinski M, Druzd-Sitek A, Orciuolo E, Li Y, Norman AD, Zaucha JM, Reis RM, Markiewicz M, Rodríguez Sevilla JJ, Andersen V, Jamroziak K, Hemminki K, Berndt SI, Rajkumar V, Mazur G, Kumar SK, Ludovico P, Nagler A, Chanock SJ, Dumontet C, Machiela MJ, Varkonyi J, Camp NJ, Ziv E, Vangsted AJ, Brown EE, Campa D, Vachon CM, Netea MG, Canzian F, Försti A, Sainz J. Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization. Int J Mol Sci 2023;24:8500. [PMID: 37239846 PMCID: PMC10218542 DOI: 10.3390/ijms24108500] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 04/10/2023] [Accepted: 04/21/2023] [Indexed: 05/28/2023] Open

Abstract

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10-9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10-4-5.79 × 10-14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10-4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10-4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10-4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3- B cells, CD5+IgD- cells, IgM- cells, IgD-IgM- cells, and CD4-CD8- PBMCs (p = 4.9 × 10-4-8.6 × 10-4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27- cells (p = 9.3 × 10-4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3-, MCP-2-, and IL20-dependent pathways.

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Affiliation(s)

Esther Clavero Hematology Department, Virgen de las Nieves University Hospital, 18012 Granada, Spain; (E.C.); (M.J.)
José Manuel Sanchez-Maldonado Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS, 18016 Granada, Spain; Instituto de Investigación Biosanataria IBs, Granada, 18014 Granada, Spain
Angelica Macauda Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.M.); (A.S.); (F.C.)
Rob Ter Horst Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; (R.T.H.); (Y.L.); (M.G.N.) CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria
Belém Sampaio-Marques Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal; (B.S.-M.); (P.L.)
Artur Jurczyszyn Plasma Cell Dyscrasias Center, Department of Hematology, Jagiellonian University Medical College, 31-066 Kraków, Poland;
Alyssa Clay-Gilmour Department of Biostatistics and Epidemiology, Arnold School of Public Health, University of South Carolina, Greenville, SC 29208, USA; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55902, USA; (A.D.N.); (C.M.V.)
Angelika Stein Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.M.); (A.S.); (F.C.)
Michelle A. T. Hildebrandt Department of Lymphoma–Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
Niels Weinhold Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Department of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, Germany
Gabriele Buda Haematology Unit, Department of Clinical and Experimental Medicine, University of Pisa/AOUP, 56126 Pisa, Italy; (G.B.); (S.G.); (E.O.)
Ramón García-Sanz Diagnostic Laboratory Unit in Hematology, University Hospital of Salamanca, IBSAL, CIBERONC, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), 37007 Salamanca, Spain; (R.G.-S.); (M.E.S.)
Waldemar Tomczak Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-059 Lublin, Poland;
Ulla Vogel National Research Centre for the Working Environment, DK-2100 Copenhagen, Denmark;
Andrés Jerez Department of Hematology, Experimental Hematology Unit, Vall d’Hebron Institute of Oncology (VHIO), University Hospital Vall d’Hebron, 08035 Barcelona, Spain;
Daria Zawirska Department of Hematology, University Hospital, 30-688 Kraków, Poland;
Marzena Wątek Holycross Medical Oncology Center, 25-735 Kielce, Poland; Institute of Hematology and Transfusion Medicine, 00-791 Warsaw, Poland
Jonathan N. Hofmann Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; (J.N.H.); (S.I.B.); (S.J.C.); (M.J.M.)
Stefano Landi Department of Biology, University of Pisa, 56126 Pisa, Italy; (S.L.); (D.C.)
John J. Spinelli Division of Population Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Aleksandra Butrym Department of Cancer Prevention and Therapy, Wroclaw Medical University, 50-367 Wroclaw, Poland; Alfred Sokolowski Specialist Hospital in Walbrzych Oncology Support Centre for Clinical Trials, 58-309 Walbrzych, Poland
Abhishek Kumar Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Manipal Academy of Higher Education (MAHE), Manipal 576104, India
Joaquín Martínez-López Hospital 12 de Octubre, Complutense University, CNIO, CIBERONC, 28041 Madrid, Spain;
Sara Galimberti Haematology Unit, Department of Clinical and Experimental Medicine, University of Pisa/AOUP, 56126 Pisa, Italy; (G.B.); (S.G.); (E.O.)
María Eugenia Sarasquete Diagnostic Laboratory Unit in Hematology, University Hospital of Salamanca, IBSAL, CIBERONC, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), 37007 Salamanca, Spain; (R.G.-S.); (M.E.S.)
Edyta Subocz Department of Hematology, Military Institute of Medicine, 04-141 Warsaw, Poland;
Elzbieta Iskierka-Jażdżewska Department of Hematology, Medical University of Lodz, 90-419 Lodz, Poland;
Graham G. Giles Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC 3004, Australia; Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3010, Australia Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia
Malwina Rybicka-Ramos Department of Hematology, Specialist Hospital No. 1 in Bytom, Academy of Silesia, Faculty of Medicine, 40-055 Katowice, Poland;
Marcin Kruszewski Department of Hematology, University Hospital No. 2, 85-168 Bydgoszcz, Poland;
Niels Abildgaard Department of Hematology, Odense University Hospital, DK-5000 Odense, Denmark;
Francisco García Verdejo Department of Medical Oncology, Complejo Hospitalario de Jaén, 23007 Jaén, Spain; (F.G.V.); (P.S.R.)
Pedro Sánchez Rovira Department of Medical Oncology, Complejo Hospitalario de Jaén, 23007 Jaén, Spain; (F.G.V.); (P.S.R.)
Miguel Inacio da Silva Filho Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany;
Katalin Kadar St Johns Hospital, 62769 Budapest, Hungary;
Małgorzata Razny Department of Hematology, Rydygier Hospital, 31-826 Cracow, Poland;
Wendy Cozen Division of Hematology/Oncology, Department of Medicine, School of Medicine, Department of Pathology, School of Medicine, Susan and Henry Samueli College of Health Sciences, Chao Family Comprehensive Cancer Center, University of California at Irvine, Irvine, CA 92697, USA;
Matteo Pelosini U.O. Dipartimento di Ematologia, Azienda USL Toscana Nord Ovest, 57124 Livorno, Italy;
Manuel Jurado Hematology Department, Virgen de las Nieves University Hospital, 18012 Granada, Spain; (E.C.); (M.J.) Instituto de Investigación Biosanataria IBs, Granada, 18014 Granada, Spain Department of Medicine, University of Granada, 18012 Granada, Spain
Parveen Bhatti Cancer Control Research, BC Cancer, Vancouver, BC V5Z 4E6, Canada; Program in Epidemiology, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Marek Dudzinski Department of Hematology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow, 35-310 Rzeszow, Poland; (M.D.); (M.M.)
Agnieszka Druzd-Sitek Department of Lymphoproliferative Diseases, Maria Skłodowska Curie National Research Institute of Oncology, 02-781 Warsaw, Poland;
Enrico Orciuolo Haematology Unit, Department of Clinical and Experimental Medicine, University of Pisa/AOUP, 56126 Pisa, Italy; (G.B.); (S.G.); (E.O.)
Yang Li Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; (R.T.H.); (Y.L.); (M.G.N.) Centre for Individualised Infection Medicine (CiiM) & TWINCORE, Joint Ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, Germany
Aaron D. Norman Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55902, USA; (A.D.N.); (C.M.V.) Genetic Epidemiology and Risk Assessment Program, Mayo Clinic Comprehensive Cancer Center, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55902, USA
Jan Maciej Zaucha Department of Hematology and Transplantology, Medical University of Gdansk, 80-210 Gdansk, Poland;
Rui Manuel Reis Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal and ICVS/3B’s-PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, Brazil
Miroslaw Markiewicz Department of Hematology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow, 35-310 Rzeszow, Poland; (M.D.); (M.M.)
Juan José Rodríguez Sevilla Department of Hematology, Hospital del Mar, 08003 Barcelona, Spain;
Vibeke Andersen Molecular Diagnostics and Clinical Research Unit, Institute of Regional Health Research, University Hospital of Southern Denmark, DK-6200 Aabenraa, Denmark;
Krzysztof Jamroziak Department of Hematology, Transplantology and Internal Medicine, Medical University of Warsaw, 02-097 Warsaw, Poland;
Kari Hemminki Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, 30605 Pilsen, Czech Republic
Sonja I. Berndt Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; (J.N.H.); (S.I.B.); (S.J.C.); (M.J.M.)
Vicent Rajkumar Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55902, USA; (V.R.); (S.K.K.)
Grzegorz Mazur Department of Internal Diseases, Occupational Medicine, Hypertension and Clinical Oncology, Wroclaw Medical University, 50-368 Wroclaw, Poland;
Shaji K. Kumar Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55902, USA; (V.R.); (S.K.K.)
Paula Ludovico Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal; (B.S.-M.); (P.L.)
Arnon Nagler Hematology Division, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel;
Stephen J. Chanock Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; (J.N.H.); (S.I.B.); (S.J.C.); (M.J.M.)
Charles Dumontet UMR INSERM 1052/CNRS 5286, University of Lyon, Hospices Civils de Lyon, 69008 Lyon, France;
Mitchell J. Machiela Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; (J.N.H.); (S.I.B.); (S.J.C.); (M.J.M.)
Judit Varkonyi Semmelweis University, 1083 Budapest, Hungary;
Nicola J. Camp Division of Hematology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA;
Elad Ziv Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94143, USA;
Annette Juul Vangsted Department of Hematology, Rigshospitalet, Copenhagen University, DK-2100 Copenhagen, Denmark;
Elizabeth E. Brown Department of Pathology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA;
Daniele Campa Department of Biology, University of Pisa, 56126 Pisa, Italy; (S.L.); (D.C.)
Celine M. Vachon Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55902, USA; (A.D.N.); (C.M.V.)
Mihai G. Netea Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; (R.T.H.); (Y.L.); (M.G.N.) Department for Immunology & Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany
Federico Canzian Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.M.); (A.S.); (F.C.)
Asta Försti Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; Hopp Children’s Cancer Center (KiTZ), 69120 Heidelberg, Germany
Juan Sainz Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS, 18016 Granada, Spain; Instituto de Investigación Biosanataria IBs, Granada, 18014 Granada, Spain Department of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, Spain

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Sanati M, Binabaj MM, Ahmadi SS, Aminyavari S, Javid H, Mollazadeh H, Bibak B, Mohtashami E, Jamialahmadi T, Afshari AR, Sahebkar A. Recent advances in glioblastoma multiforme therapy: A focus on autophagy regulation. Biomed Pharmacother 2022;155:113740. [PMID: 36166963 DOI: 10.1016/j.biopha.2022.113740] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/14/2022] [Accepted: 09/21/2022] [Indexed: 11/02/2022] Open

Affiliation(s)

Mehdi Sanati Department of Pharmacology and Toxicology, Faculty of Pharmacy, Birjand University of Medical Sciences, Birjand, Iran; Experimental and Animal Study Center, Birjand University of Medical Sciences, Birjand, Iran
Maryam Moradi Binabaj Non-Communicable Diseases Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
Seyed Sajad Ahmadi Department of Physiology and Pharmacology, Faculty of Medicine, North Khorasan ‎University of Medical Sciences, Bojnurd, Iran
Samaneh Aminyavari Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
Hossein Javid Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
Hamid Mollazadeh Department of Physiology and Pharmacology, Faculty of Medicine, North Khorasan ‎University of Medical Sciences, Bojnurd, Iran
Bahram Bibak Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
Elmira Mohtashami Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
Tannaz Jamialahmadi Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Amir R Afshari Department of Physiology and Pharmacology, Faculty of Medicine, North Khorasan ‎University of Medical Sciences, Bojnurd, Iran; Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran.
Amirhossein Sahebkar Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

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Autophagy in Hematological Malignancies. Cancers (Basel) 2022;14:cancers14205072. [PMID: 36291856 PMCID: PMC9600546 DOI: 10.3390/cancers14205072] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 10/10/2022] [Accepted: 10/13/2022] [Indexed: 11/29/2022] Open

Abstract

Simple Summary

Autophagy is a dynamic and tightly regulated process that seems to have dual effects in cancer. In some contexts, it can induce carcinogenesis and promote cancer cell survival, whereas in others, it acts preventing tumor cell growth and tumor progression. Thus, autophagy functions seem to strictly depend on cancer ontogenesis, progression, and type. Here, we will dive into the current knowledge of autophagy in hematological malignancies and will highlight the main genetic components involved in each cancer type.

Abstract

Autophagy is a highly conserved metabolic pathway via which unwanted intracellular materials, such as unfolded proteins or damaged organelles, are digested. It is activated in response to conditions of oxidative stress or starvation, and is essential for the maintenance of cellular homeostasis and other vital functions, such as differentiation, cell death, and the cell cycle. Therefore, autophagy plays an important role in the initiation and progression of tumors, including hematological malignancies, where damaged autophagy during hematopoiesis can cause malignant transformation and increase cell proliferation. Over the last decade, the importance of autophagy in response to standard pharmacological treatment of hematological tumors has been observed, revealing completely opposite roles depending on the tumor type and stage. Thus, autophagy can promote tumor survival by attenuating the cellular damage caused by drugs and/or stabilizing oncogenic proteins, but can also have an antitumoral effect due to autophagic cell death. Therefore, autophagy-based strategies must depend on the context to create specific and safe combination therapies that could contribute to improved clinical outcomes. In this review, we describe the process of autophagy and its role on hematopoiesis, and we highlight recent research investigating its role as a potential therapeutic target in hematological malignancies. The findings suggest that genetic variants within autophagy-related genes modulate the risk of developing hemopathies, as well as patient survival.

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Chen Y, Li Q, Ren S, Chen T, Zhai B, Cheng J, Shi X, Song L, Fan Y, Guo D. Investigation and experimental validation of curcumin-related mechanisms against hepatocellular carcinoma based on network pharmacology. J Zhejiang Univ Sci B 2022;23:682-698. [PMID: 35953761 PMCID: PMC9381327 DOI: 10.1631/jzus.b2200038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 04/27/2022] [Indexed: 11/11/2022]

Abstract

OBJECTIVES

To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma (HCC) by network pharmacology and experimental in vitro validation.

METHODS

The predictive targets of curcumin or HCC were collected from several databases. the identified overlapping targets were crossed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Two of the candidate pathways were selected to conduct an experimental verification. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay was used to determine the effect of curcumin on the viability of HepG2 and LO2 cells. The apoptosis and autophagy of HepG2 cells were respectively detected by flow cytometry and transmission electron microscopy. Besides, western blot and real-time polymerase chain reaction (PCR) were employed to verify the p53 apoptotic pathway and adenosine 5'-monophosphate (AMP)‍-activated protein kinase (AMPK) autophagy pathway. HepG2 cells were pretreated with pifithrin-‍α (PFT-‍α) and GSK690693 for further investigation.

RESULTS

The 167 pathways analyzed by KEGG included apoptosis, autophagy, p53, and AMPK pathways. The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug, regulation of apoptotic pathway, and so on. The in vitro experiments also confirmed that curcumin can inhibit the growth of HepG2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway. Furthermore, the protein and messenger RNA (mRNA) of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group. The damage-regulated autophagy modulator (DRAM) in the PFT-‍α-pretreated group was downregulated, and p62 in the GSK690693-pretreated group was upregulated.

CONCLUSIONS

Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1 (ULK1) autophagy pathway, in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.

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Interleukin 7 inhibit autophagy via P53 regulated AMPK/mTOR signaling pathway in non-small cell lung cancer. Sci Rep 2022;12:11208. [PMID: 35778432 PMCID: PMC9249745 DOI: 10.1038/s41598-022-14742-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Accepted: 06/13/2022] [Indexed: 11/15/2022] Open

Chai D, Shi SY, Sobhani N, Ding J, Zhang Z, Jiang N, Wang G, Li M, Li H, Zheng J, Bai J. IFI35 Promotes Renal Cancer Progression by Inhibiting pSTAT1/pSTAT6-Dependent Autophagy. Cancers (Basel) 2022;14:cancers14122861. [PMID: 35740527 PMCID: PMC9221357 DOI: 10.3390/cancers14122861] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 06/06/2022] [Accepted: 06/07/2022] [Indexed: 02/04/2023] Open

Affiliation(s)

Dafei Chai Cancer Institute, Xuzhou Medical University, Xuzhou 221002, China; (D.C.); (J.D.); (Z.Z.); (N.J.); (G.W.); (M.L.) Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou 221002, China Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, TX 77030, USA;
Shang Yuchen Shi Department of Stereotactic Radiotherapy, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China;
Navid Sobhani Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, TX 77030, USA;
Jiage Ding Cancer Institute, Xuzhou Medical University, Xuzhou 221002, China; (D.C.); (J.D.); (Z.Z.); (N.J.); (G.W.); (M.L.) Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou 221002, China
Zichun Zhang Cancer Institute, Xuzhou Medical University, Xuzhou 221002, China; (D.C.); (J.D.); (Z.Z.); (N.J.); (G.W.); (M.L.) Department of Urology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China;
Nan Jiang Cancer Institute, Xuzhou Medical University, Xuzhou 221002, China; (D.C.); (J.D.); (Z.Z.); (N.J.); (G.W.); (M.L.) Department of Urology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China;
Gang Wang Cancer Institute, Xuzhou Medical University, Xuzhou 221002, China; (D.C.); (J.D.); (Z.Z.); (N.J.); (G.W.); (M.L.) Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou 221002, China
Minle Li Cancer Institute, Xuzhou Medical University, Xuzhou 221002, China; (D.C.); (J.D.); (Z.Z.); (N.J.); (G.W.); (M.L.) Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou 221002, China
Hailong Li Department of Urology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China;
Junnian Zheng Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou 221002, China Correspondence: (J.Z.); (J.B.)
Jin Bai Cancer Institute, Xuzhou Medical University, Xuzhou 221002, China; (D.C.); (J.D.); (Z.Z.); (N.J.); (G.W.); (M.L.) Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou 221002, China Correspondence: (J.Z.); (J.B.)

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Abdelhamid AM, Saber S, Youssef ME, Gaafar AGA, Eissa H, Abd-Eldayem MA, Alqarni M, Batiha GES, Obaidullah AJ, Shahien MA, El-Ahwany E, Amin NA, Etman MA, Kaddah MMY, Abd El-Fattah EE. Empagliflozin adjunct with metformin for the inhibition of hepatocellular carcinoma progression: Emerging approach for new application. Biomed Pharmacother 2021;145:112455. [PMID: 34844106 DOI: 10.1016/j.biopha.2021.112455] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/05/2021] [Accepted: 11/16/2021] [Indexed: 02/08/2023] Open

Abstract

Hepatocellular carcinoma (HCC) is on the rise worldwide, and its incidence in diabetic patients is two to three times that of non-diabetics. Current therapeutic options fail to provide considerable survival benefits to patients with HCC. There is a strong possibility that the FDA-approved antidiabetic combination of empagliflozin and metformin could show complementary effects to control HCC progression. However, their multitarget effects have not yet been studied on HCC development. Therefore, the present study aims to evaluate the antitumorigenic activity of this combination in non-diabetic mice with diethylnitrosamine-induced HCC. Empagliflozin/metformin combination prolonged survival and improved histological features of mice livers. Additionally, Empagliflozin/metformin showed anti-inflammatory potential and relieved oxidative stress. On the one hand these effects are likely attributed to the ability of metformin to inactivate NF-κB in an AMPK-dependent mechanism and on the other hand to the ability of the empagliflozin to inhibit the MAPKs, p38 and ERK1/2. Empagliflozin also showed a less robust effect on AMPK than that of metformin. Moreover, empagliflozin enhanced the autophagy inducing activity of metformin. Furthermore, empagliflozin/metformin exhibited increased apoptotic potential. Consequently, empagliflozin augmented the antitumorigenic function of metformin by exerting better control of angiogenesis, and metastasis. To conclude, our findings suggest empagliflozin as an ideal adjunct to metformin for the inhibition of HCC progression. In addition, since the incidence of hypoglycemia is minimal due to insulin-independent mechanism of action of both treatments, empagliflozin/metformin could be a promising therapeutic modality for the management of diabetic patients with HCC; and even non diabetic ones.

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Affiliation(s)

Amir Mohamed Abdelhamid Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt
Sameh Saber Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt.
Mahmoud E Youssef Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt
Ahmed Gaafar Ahmed Gaafar Department of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University, Port Said, Egypt
Hanan Eissa Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Marwa A Abd-Eldayem Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Horus University, New Damietta, Egypt
Mohammed Alqarni Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Gaber El-Saber Batiha Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, Egypt
Ahmad J Obaidullah Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Mohamed Awad Shahien Department of Clinical Pharmacology, Faculty of Medicine, Damietta University, Damietta, Egypt
Eman El-Ahwany Department of Immunology, Theodor Bilharz Research Institute, Giza, Egypt
Noha A Amin Department of Hematology, Theodor Bilharz Research Institute, Giza, Egypt
Mohamed Ali Etman Research and Development, Department of Drug Stability, Safe Pharma, Pharco Pharmaceuticals, Alexandria, Egypt
Mohamed M Y Kaddah Pharmaceutical and Fermentation Industries Development Center, City of Scientific Research and Technological Applications, New Borg El-Arab 21934, Alexandria, Egypt
Eslam E Abd El-Fattah Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt

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Chen L, He M, Zhang M, Sun Q, Zeng S, Zhao H, Yang H, Liu M, Ren S, Meng X, Xu H. The Role of non-coding RNAs in colorectal cancer, with a focus on its autophagy. Pharmacol Ther 2021;226:107868. [PMID: 33901505 DOI: 10.1016/j.pharmthera.2021.107868] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 04/16/2021] [Accepted: 04/20/2021] [Indexed: 02/06/2023]

Affiliation(s)

Li Chen State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Man He State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Meng Zhang State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Qiang Sun State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Sha Zeng State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Hui Zhao State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Han Yang State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Maolun Liu State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Shan Ren State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Xianli Meng State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Haibo Xu State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

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So KY, Park BH, Oh SH. Cytoplasmic sirtuin 6 translocation mediated by p62 polyubiquitination plays a critical role in cadmium-induced kidney toxicity. Cell Biol Toxicol 2021;37:193-207. [PMID: 32394328 DOI: 10.1007/s10565-020-09528-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 04/15/2020] [Indexed: 12/22/2022]

Li J, Pu K, Li C, Wang Y, Zhou Y. A Novel Six-Gene-Based Prognostic Model Predicts Survival and Clinical Risk Score for Gastric Cancer. Front Genet 2021;12:615834. [PMID: 33692828 PMCID: PMC7938863 DOI: 10.3389/fgene.2021.615834] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 01/15/2021] [Indexed: 12/24/2022] Open

Abstract

Background: Autophagy plays a vital role in cancer initiation, malignant progression, and resistance to treatment. However, autophagy-related genes (ARGs) have rarely been analyzed in gastric cancer (GC). The purpose of this study was to analyze ARGs in GC using bioinformatic analysis and to identify new biomarkers for predicting the overall survival (OS) of patients with GC.

Methods: The gene expression profiles and clinical data of patients with GC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, and ARGs were obtained from two other datasets (the Human Autophagy Database and Molecular Signatures Database). Lasso, univariate, and multivariate Cox regression analyses were performed to identify the OS-related ARGs. Finally, a six-ARG model was identified as a prognostic indicator using the risk-score model, and survival and prognostic performance were analyzed based on the Kaplan-Meier test and ROC curve. Estimate calculations were used to assess the immune status of this model, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed for investigating the functions and terms associated with the model-related genes in GC.

Results: The six ARGs, DYNLL1, PGK2, HPR, PLOD2, PHYHIP, and CXCR4, were identified using Lasso and Cox regression analyses. Survival analysis revealed that the OS of GC patients in the high-risk group was significantly lower than that of the low-risk group (p < 0.05). The ROC curves revealed that the risk score model exhibited better prognostic performance with respect to OS. Multivariate Cox regression analysis indicated that the model was an independent predictor of OS and was not affected by most of the clinical traits (p < 0.05). The model-related genes were associated with immune suppression and several biological process terms, such as extracellular structure organization and matrix organization. Moreover, the genes were associated with the P13K-Akt signaling pathway, focal adhesion, and MAPK signaling pathway.

Conclusions: This study presents potential prognostic biomarkers for GC patients that would aid in determining the best patient-specific course of treatment.

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He YH, Tian G. Autophagy as a Vital Therapy Target for Renal Cell Carcinoma. Front Pharmacol 2021;11:518225. [PMID: 33643028 PMCID: PMC7902926 DOI: 10.3389/fphar.2020.518225] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Accepted: 12/23/2020] [Indexed: 12/30/2022] Open

Mishra RK, Ahmad A, Vyawahare A, Kumar A, Khan R. Understanding the Monoclonal Antibody Involvement in Targeting the Activation of Tumor Suppressor Genes. Curr Top Med Chem 2020;20:1810-1823. [PMID: 32543361 DOI: 10.2174/1568026620666200616133814] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 04/28/2020] [Accepted: 05/08/2020] [Indexed: 12/14/2022]

Abstract Monoclonal antibodies (mAbs) have always provided outstanding therapeutic arsenal in the treatment of cancer, be it hematological malignancies or solid tumors. Monoclonal antibodies mediated targeting of cancer genes in general and tumor-suppressor genes, in particular, have appreciably allowed the possibilities of trafficking these antibodies to specific tumor mechanisms and aim for the pin-point maneuvered tumor treatment strategies. The conventional cancer treatment options are associated with enormous limitations like drug resistance, acute and pan-toxic side effects and collateral damage to other unrelated cells and organs. Therefore, monoclonal antibody-mediated treatments have some special advantages of specific targeting of cancer-related genes and minimizing the off-target side effects. A large number of monoclonal antibody-mediated treatment regimen viz. use of immunoconjugates, clinically targeting TGFβ with pan-TGFβ monoclonal antibodies, p53 by its monoclonal antibodies and EGFRtargeted monoclonal antibodies, etc. have been observed in the recent past. In this review, the authors have discussed some of the significant advances in the context of targeting tumor suppressor genes with monoclonal antibodies. Approximately 250 articles were scanned from research databases like PubMed central, Europe PubMed Central and google scholar up to the date of inception, and relevant reports on monoclonal antibody-mediated targeting of cancer genes were selected. mAb mediated targeting of tumor suppressor genes is a recent grey paradigm, which has not been explored up to its maximum potential. Therefore, this review will be of appreciable significance that it will boost further in-depth understanding of various aspects of mAb arbitrated cancer targeting and will warrant and promote further rigorous research initiatives in this regard. The authors expect that this review will acquaint the readers with the current status regarding the recent progress in the domain of mAbs and their employability and targetability towards tumor suppressor genes in anti-cancer therapeutics. Collapse

Tian H, Wang W, Meng X, Wang M, Tan J, Jia W, Li P, Li J, Zhou Q. ERas Enhances Resistance to Cisplatin-Induced Apoptosis by Suppressing Autophagy in Gastric Cancer Cell. Front Cell Dev Biol 2020;7:375. [PMID: 32083074 PMCID: PMC7005724 DOI: 10.3389/fcell.2019.00375] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 12/16/2019] [Indexed: 12/24/2022] Open

Yang Y, Shu X, Shu XO, Bolla MK, Kweon SS, Cai Q, Michailidou K, Wang Q, Dennis J, Park B, Matsuo K, Kwong A, Park SK, Wu AH, Teo SH, Iwasaki M, Choi JY, Li J, Hartman M, Shen CY, Muir K, Lophatananon A, Li B, Wen W, Gao YT, Xiang YB, Aronson KJ, Spinell JJ, Gago-Dominguez M, John EM, Kurian AW, Chang-Claude J, Chen ST, Dörk T, Evans DGR, Schmidt MK, Shin MH, Giles GG, Milne RL, Simard J, Kubo M, Kraft P, Kang D, Easton DF, Zheng W, Long J. Re-evaluating genetic variants identified in candidate gene studies of breast cancer risk using data from nearly 280,000 women of Asian and European ancestry. EBioMedicine 2019;48:203-211. [PMID: 31629678 PMCID: PMC6838373 DOI: 10.1016/j.ebiom.2019.09.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 08/30/2019] [Accepted: 09/05/2019] [Indexed: 12/24/2022] Open

Affiliation(s)

Yaohua Yang Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
Xiang Shu Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
Xiao-Ou Shu Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
Manjeet K Bolla Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
Sun-Seog Kweon Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea
Qiuyin Cai Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
Kyriaki Michailidou Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
Qin Wang Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
Joe Dennis Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
Boyoung Park Department of Medicine, College of Medicine, Hanyang University, Seoul, South Korea
Keitaro Matsuo Department of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
Ava Kwong Hong Kong Hereditary Breast Cancer Family Registry, Happy Valley, Hong Kong; Department of Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong; Department of Surgery, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong
Sue Kyung Park Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
Anna H Wu Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Soo Hwang Teo Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia; Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia
Motoki Iwasaki Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
Ji-Yeob Choi Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea
Jingmei Li Human Genetics, Genome Institute of Singapore, Singapore; Department of Surgery, National University Hospital, Singapore
Mikael Hartman Department of Surgery, National University Hospital, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore
Chen-Yang Shen School of Public Health, China Medical University, Taichung, Taiwan; Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
Kenneth Muir Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK; Institute of Population Health, University of Manchester, Manchester, UK
Artitaya Lophatananon Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK; Institute of Population Health, University of Manchester, Manchester, UK
Bingshan Li Department of Molecular Physiology & Biophysics, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA
Wanqing Wen Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
Yu-Tang Gao Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
Yong-Bing Xiang State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Kristan J Aronson Department of Public Health Sciences, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
John J Spinell Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
Manuela Gago-Dominguez Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago De Compostela, Spain; Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
Esther M John Department of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, USA; Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
Allison W Kurian Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
Jenny Chang-Claude Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Shou-Tung Chen Division of General Surgery, Changhua Christian Hospital, Changhua, Taiwan
Thilo Dörk Gynaecology Research Unit, Hannover Medical School, Hannover, Germany
D Gareth R Evans Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK; Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK
Marjanka K Schmidt Division of Molecular Pathology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands
Min-Ho Shin Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea
Graham G Giles Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
Roger L Milne Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
Jacques Simard Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Quebec, Canada
Michiaki Kubo RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Peter Kraft Program in Genetic Epidemiology and Statistical Genetics, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
Daehee Kang Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
Douglas F Easton Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
Wei Zheng Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
Jirong Long Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.

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AMPK: A promising molecular target for combating cisplatin toxicities. Biochem Pharmacol 2019;163:94-100. [DOI: 10.1016/j.bcp.2019.02.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Accepted: 02/05/2019] [Indexed: 02/07/2023]

Escobar KA, Cole NH, Mermier CM, VanDusseldorp TA. Autophagy and aging: Maintaining the proteome through exercise and caloric restriction. Aging Cell 2019;18:e12876. [PMID: 30430746 PMCID: PMC6351830 DOI: 10.1111/acel.12876] [Citation(s) in RCA: 150] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 08/31/2018] [Accepted: 09/28/2018] [Indexed: 12/16/2022] Open

Cao Y, Luo Y, Zou J, Ouyang J, Cai Z, Zeng X, Ling H, Zeng T. Autophagy and its role in gastric cancer. Clin Chim Acta 2018;489:10-20. [PMID: 30472237 DOI: 10.1016/j.cca.2018.11.028] [Citation(s) in RCA: 118] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 11/17/2018] [Accepted: 11/20/2018] [Indexed: 02/08/2023]

Affiliation(s)

Yijing Cao Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China), College of Hunan Province, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, PR China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study [Hunan Provincial Education Department document (Approval number: 2014-405)], Hengyang, Hunan 421001, PR China
Yichen Luo Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China), College of Hunan Province, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, PR China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study [Hunan Provincial Education Department document (Approval number: 2014-405)], Hengyang, Hunan 421001, PR China
Juan Zou Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China), College of Hunan Province, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, PR China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study [Hunan Provincial Education Department document (Approval number: 2014-405)], Hengyang, Hunan 421001, PR China
Jun Ouyang Department of Gastrointestinal Surgery, the First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, PR China
Zhihong Cai Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China), College of Hunan Province, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, PR China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study [Hunan Provincial Education Department document (Approval number: 2014-405)], Hengyang, Hunan 421001, PR China
Xi Zeng Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China), College of Hunan Province, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, PR China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study [Hunan Provincial Education Department document (Approval number: 2014-405)], Hengyang, Hunan 421001, PR China
Hui Ling Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China), College of Hunan Province, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, PR China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study [Hunan Provincial Education Department document (Approval number: 2014-405)], Hengyang, Hunan 421001, PR China.
Tiebing Zeng Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study [Hunan Provincial Education Department document (Approval number: 2014-405)], Hengyang, Hunan 421001, PR China; Institute of Pathogenic Biology, Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China.

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Ciechomska IA, Marciniak MP, Jackl J, Kaminska B. Pre-treatment or Post-treatment of Human Glioma Cells With BIX01294, the Inhibitor of Histone Methyltransferase G9a, Sensitizes Cells to Temozolomide. Front Pharmacol 2018;9:1271. [PMID: 30450051 PMCID: PMC6224489 DOI: 10.3389/fphar.2018.01271] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 10/18/2018] [Indexed: 12/15/2022] Open

Abstract

Glioblastoma (GBM) is a malignant, primary brain tumor, highly resistant to conventional therapies. Temozolomide (TMZ) is a first line therapeutic agent in GBM patients, however, survival of such patients is poor. High level of DNA repair protein, O⁶-methylguanine-DNA-methyltransferase (MGMT) and occurrence of glioma stem-like cells contribute to GBM resistance to the drug. Here, we explored a possibility of epigenetic reprograming of glioma cells to increase sensitivity to TMZ and restore apoptosis competence. We combined TMZ treatment with BIX01294, an inhibitor of histone methyltransferase G9a, known to be involved in cancerogenesis. Two treatment combinations were tested: BIX01294 was administered to human LN18 and U251 glioma cell cultures 48 h before TMZ or 48 h after TMZ treatment. Despite their different status of the MGMT gene promoter, there was no correlation with the response to TMZ. The analyses of cell viability, appearance of apoptotic alterations in morphology of cells and nuclei, and markers of apoptosis, such as levels of cleaved caspase 3, caspase 7 and PARP, revealed that both pre-treatment and post-treatment with BIX01294 sensitize glioma cells to TMZ. The additive effect was stronger in LN18 cells. Moreover, BIX01294 enhanced the cytotoxic effect of TMZ on glioma stem-like cells, although it was not associated with modulation of the pluripotency markers (NANOG, SOX2, CD133) expression or methylation of NANOG and SOX2 gene promoters. Accordingly, knockdown of methyltransferase G9a augments TMZ-induced cell death in LN18 cells. We found the significant increases of the LC3-II levels in LN18 cells treated with BIX01294 alone and with drug combination that suggests involvement of autophagy in enhancement of anti-tumor effect of TMZ. Treatment with BIX01294 did not affect methylation of the MGMT gene promoter. Altogether, our results suggest that G9a is a potential therapeutic target in malignant glioma and the treatment with the G9a inhibitor reprograms glioma cells and glioma stem-like cells to increase sensitivity to TMZ and restore apoptosis competence.

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AIM2 is a potential therapeutic target in human renal carcinoma and suppresses its invasion and metastasis via enhancing autophagy induction. Exp Cell Res 2018;370:561-570. [DOI: 10.1016/j.yexcr.2018.07.021] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 07/11/2018] [Accepted: 07/12/2018] [Indexed: 12/19/2022]

Pierzynowska K, Gaffke L, Cyske Z, Puchalski M, Rintz E, Bartkowski M, Osiadły M, Pierzynowski M, Mantej J, Piotrowska E, Węgrzyn G. Autophagy stimulation as a promising approach in treatment of neurodegenerative diseases. Metab Brain Dis 2018;33:989-1008. [PMID: 29542037 PMCID: PMC6060747 DOI: 10.1007/s11011-018-0214-6] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 03/08/2018] [Indexed: 12/19/2022]

Pawlowska E, Szczepanska J, Szatkowska M, Blasiak J. An Interplay between Senescence, Apoptosis and Autophagy in Glioblastoma Multiforme-Role in Pathogenesis and Therapeutic Perspective. Int J Mol Sci 2018;19:ijms19030889. [PMID: 29562589 PMCID: PMC5877750 DOI: 10.3390/ijms19030889] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 03/14/2018] [Accepted: 03/15/2018] [Indexed: 12/12/2022] Open

Subramanian G, Kuzmanovic T, Zhang Y, Peter CB, Veleeparambil M, Chakravarti R, Sen GC, Chattopadhyay S. A new mechanism of interferon's antiviral action: Induction of autophagy, essential for paramyxovirus replication, is inhibited by the interferon stimulated gene, TDRD7. PLoS Pathog 2018;14:e1006877. [PMID: 29381763 PMCID: PMC5806901 DOI: 10.1371/journal.ppat.1006877] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Revised: 02/09/2018] [Accepted: 01/12/2018] [Indexed: 12/14/2022] Open

Abstract

The interferon (IFN) system represents the first line of defense against a wide range of viruses. Virus infection rapidly triggers the transcriptional induction of IFN-β and IFN Stimulated Genes (ISGs), whose protein products act as viral restriction factors by interfering with specific stages of virus life cycle, such as entry, transcription, translation, genome replication, assembly and egress. Here, we report a new mode of action of an ISG, IFN-induced TDRD7 (tudor domain containing 7) inhibited paramyxovirus replication by inhibiting autophagy. TDRD7 was identified as an antiviral gene by a high throughput screen of an ISG shRNA library for blocking IFN’s protective effect against Sendai virus (SeV) replication. The antiviral activity of TDRD7 against SeV, human parainfluenza virus 3 and respiratory syncytial virus was confirmed by its genetic ablation or ectopic expression in several types of mouse and human cells. TDRD7’s antiviral action was mediated by its ability to inhibit autophagy, a cellular catabolic process which was robustly induced by SeV infection and required for its replication. Mechanistic investigation revealed that TDRD7 interfered with the activation of AMP-dependent kinase (AMPK), an enzyme required for initiating autophagy. AMPK activity was required for efficient replication of several paramyxoviruses, as demonstrated by its genetic ablation or inhibition of its activity by TDRD7 or chemical inhibitors. Therefore, our study has identified a new antiviral ISG with a new mode of action.

The antiviral functions of interferons (IFNs) are mediated by the IFN-induced proteins, encoded by the IFN Stimulated Genes (ISGs). Because ISGs are virus-specific, we performed a high throughput genetic screen to identify novel antiviral ISGs against Sendai virus (SeV), a respirovirus of the Paramyxoviridae family. Our screen isolated a small subset of anti-SeV ISGs, among which we focused on a novel ISG, Tudor domain containing 7 (TDRD7). The antiviral activity of TDRD7 was confirmed by genetic ablation of the endogenous, and the ectopic expression of the exogenous, TDRD7 in human and mouse cell types. Investigation of the mechanism of antiviral action revealed that TDRD7 inhibited ‘virus-induced autophagy’, which was required for the replication of SeV. Autophagy, a cellular catabolic process, was robustly induced by SeV infection, and was inhibited by TDRD7. TDRD7 interfered with the ‘induction’ step of autophagy by inhibiting the activation of AMP-dependent Kinase (AMPK). AMPK is a multifunctional metabolic kinase, which was activated by SeV infection, and its activity was required for virus replication. Genetic ablation and inhibition of AMPK activity by physiological (TDRD7) or chemical (Compound C) inhibitors strongly attenuated SeV replication. The anti-AMPK activity of TDRD7 was capable of inhibiting other members of Paramyxoviridae family, human parainfluenza virus type 3 and respiratory syncytial virus. Therefore, our study uncovered a new antiviral mechanism of IFN by inhibiting the activation of autophagy-inducing kinase AMPK.

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Paquette M, El-Houjeiri L, Pause A. mTOR Pathways in Cancer and Autophagy. Cancers (Basel) 2018;10:cancers10010018. [PMID: 29329237 PMCID: PMC5789368 DOI: 10.3390/cancers10010018] [Citation(s) in RCA: 213] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Revised: 12/22/2017] [Accepted: 01/09/2018] [Indexed: 12/11/2022] Open

Chang H, Li X, Cai Q, Li C, Tian L, Chen J, Xing X, Gan Y, Ouyang W, Yang Z. The PI3K/Akt/mTOR pathway is involved in CVB3-induced autophagy of HeLa cells. Int J Mol Med 2017;40:182-192. [PMID: 28560385 PMCID: PMC5466389 DOI: 10.3892/ijmm.2017.3008] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Accepted: 05/26/2017] [Indexed: 12/19/2022] Open

Xu F, Fang Y, Yan L, Xu L, Zhang S, Cao Y, Xu L, Zhang X, Xie J, Jiang G, Ge C, An N, Zhou D, Yuan N, Wang J. Nuclear localization of Beclin 1 promotes radiation-induced DNA damage repair independent of autophagy. Sci Rep 2017;7:45385. [PMID: 28345663 PMCID: PMC5366945 DOI: 10.1038/srep45385] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Accepted: 02/23/2017] [Indexed: 12/27/2022] Open

Affiliation(s)

Fei Xu Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China
Yixuan Fang Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China
Lili Yan Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China
Lan Xu Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China
Suping Zhang Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, The First Affiliated Hospital, Soochow University School of Medicine, Suzhou 215123, China Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas Medical Sciences, Little Rock, Arkansas 72205, USA
Yan Cao Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China
Li Xu Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China
Xiaoying Zhang Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China
Jialing Xie Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China
Gaoyue Jiang Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China
Chaorong Ge Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China
Ni An Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China
Daohong Zhou Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas Medical Sciences, Little Rock, Arkansas 72205, USA
Na Yuan Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, The First Affiliated Hospital, Soochow University School of Medicine, Suzhou 215123, China
Jianrong Wang Hematology Center of Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University School of Medicine, Suzhou 215123, China Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, The First Affiliated Hospital, Soochow University School of Medicine, Suzhou 215123, China

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Qu B, Yao L, Ma HL, Chen HL, Zhang Z, Xie J. Prognostic significance of autophagy-related proteins expression in resected human gastric adenocarcinoma. ACTA ACUST UNITED AC 2017;37:37-43. [PMID: 28224423 DOI: 10.1007/s11596-017-1691-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 01/10/2017] [Indexed: 12/19/2022]

Abstract

Gastric adenocarcinoma (GC) is one of the most common malignancies in the world and one of the most frequent causes of cancer-related death. Autophagy is a highly regulated catabolic pathway responsible for the degradation of long-lived proteins and damaged intracellular organelles. However, the mechanism and guiding significance of autophagy in the development and progression of GC have remained to be elucidated. This study aimed to explore the clinicopathological significances and prognostic values of autophagy-related proteins AMBRA1 and Beclin-1 in GC. Quantum dots based immunofluorescence histochemistry (QDs-IHC) was performed to observe the expression of AMBRA1 and Beclin-1 proteins in the tissue microarrays including 163 specimens of GC and 20 noncancerous gastric tissues. Simultaneously, AMBRA1 and Beclin-1 proteins were detected by Western blotting in the 10 fresh GC and corresponding normal gastric tissues. The results showed that the expression levels of both AMBRA1 and Beclin-1 proteins were higher in GC tissues than in noncancerous gastric tissues by QDs-IHC and Western blotting (P<0.05). High AMBRA1 expression was detected in 90 of 163 (55.2%) GCs and high Beclin-1 expression was detected in 83 of 163 (50.9%) GCs. High AMBRA1 expression was closely related to depth of invasion, and lymph nodes metastasis (P<0.05). High expression of Beclin-1 protein was correlated with tumor grade (P<0.05). Positive correlation was observed between AMBRA1 and Beclin-1. Survival analysis indicated the high expression of AMBRA1 and Beclin- 1 was an independent factor in predicting poor overall survival (OS) of GC patients. These findings suggest the high expression of AMBRA1 and Beclin-1 proteins is significantly correlated with GC progression. High AMBRA1 and Beclin-1 expression heralds worse outcome of GC patients, suggesting a novel candidate prognostic marker and a therapeutic target for GC.

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Long Term Culture of the A549 Cancer Cell Line Promotes Multilamellar Body Formation and Differentiation towards an Alveolar Type II Pneumocyte Phenotype. PLoS One 2016;11:e0164438. [PMID: 27792742 PMCID: PMC5085087 DOI: 10.1371/journal.pone.0164438] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 09/26/2016] [Indexed: 11/19/2022] Open

Visconte V, Przychodzen B, Han Y, Nawrocki ST, Thota S, Kelly KR, Patel BJ, Hirsch C, Advani AS, Carraway HE, Sekeres MA, Maciejewski JP, Carew JS. Complete mutational spectrum of the autophagy interactome: a novel class of tumor suppressor genes in myeloid neoplasms. Leukemia 2016;31:505-510. [PMID: 27773925 PMCID: PMC5844476 DOI: 10.1038/leu.2016.295] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]

Affiliation(s)

V Visconte Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
B Przychodzen Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
Y Han Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
S T Nawrocki Department of Medicine, Division of Translational and Regenerative Medicine, University of Arizona Cancer Center, Tucson, AZ, USA
S Thota Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
K R Kelly Department of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA
B J Patel Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
C Hirsch Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
A S Advani Leukemia Program, Department of Hematology/Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
H E Carraway Leukemia Program, Department of Hematology/Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
M A Sekeres Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.,Leukemia Program, Department of Hematology/Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
J P Maciejewski Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
J S Carew Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.,Department of Medicine, Division of Translational and Regenerative Medicine, University of Arizona Cancer Center, Tucson, AZ, USA

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Davidson SM, Vander Heiden MG. Critical Functions of the Lysosome in Cancer Biology. Annu Rev Pharmacol Toxicol 2016;57:481-507. [PMID: 27732799 DOI: 10.1146/annurev-pharmtox-010715-103101] [Citation(s) in RCA: 145] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]

Kim KH, Song HH, Ahn KS, Oh SR, Sadikot RT, Joo M. Ethanol extract of the tuber of Alisma orientale reduces the pathologic features in a chronic obstructive pulmonary disease mouse model. JOURNAL OF ETHNOPHARMACOLOGY 2016;188:21-30. [PMID: 27154406 DOI: 10.1016/j.jep.2016.05.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Revised: 04/20/2016] [Accepted: 05/02/2016] [Indexed: 06/05/2023]

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

The tuber of Alismataceae Alisma orientale Juzepzuk has been prescribed as a remedy for treating the diseases associated with body fluid dysfunction such as edema and inflammatory lung diseases. Chronic obstructive pulmonary disease (COPD) is a debilitating, inflammatory lung disease without effective treatment. Along with persistent inflammation, autophagy has been recently reported to contribute to COPD. Here, by employing a murine model, we examined whether the tuber of the plant is effective against COPD MATERIALS AND METHODS: The ethanol extract of the tuber of A. orientale Juzepzuk (EEAO) was fingerprinted by HPLC. For the establishment of COPD lung, mice received single intratracheal (i.t.) spraying of elastase and LPS per week for 2 weeks. After approximated to the dose prescribed typically to patients, EEAO was administered to the lung 2h after each LPS treatment. Morphometric analyses, semi-quantitative RT-PCR, and western blot were performed to evaluate the effects of EEAO on emphysema, inflammation, and autophagy in mouse lungs. The effect of EEAO on autophagy was also assessed by western blot at the cellular level with murine macrophages and human lung epithelial cells.

RESULTS

When receiving i.t. elastase and LPS for 2 weeks, mice developed emphysema and inflammation in the lung. EEAO treatment, however, significantly reduced emphysema and inflammatory cell infiltration to the lung with concomitant decrease of the production of pro-inflammatory cytokines including TNF-α, IL-6, and TGF-β, signature cytokines of COPD. Unlike control mice, the lungs of the COPD mice expressed LC3-II, a biomarker for autophagy formation, which was decreased by EEAO treatment. EEAO also lowered the expression of LC3-II in murine macrophage, RAW 264.7, and human lung epithelial cell, BEAS-2B, which was associated with EEAO activating mTOR.

CONCLUSION

EEAO relieved COPD pathologic features in a mouse model, which was associated with suppression of lung inflammation, emphysema, and autophagy. Our results suggest an effectiveness of the tuber of A. orientale in chronic inflammatory lung diseases such as COPD.

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Di Fazio P, Waldegger P, Jabari S, Lingelbach S, Montalbano R, Ocker M, Slater EP, Bartsch DK, Illig R, Neureiter D, Wissniowski TT. Autophagy-related cell death by pan-histone deacetylase inhibition in liver cancer. Oncotarget 2016;7:28998-29010. [PMID: 27058414 PMCID: PMC5045373 DOI: 10.18632/oncotarget.8585] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Accepted: 03/18/2016] [Indexed: 02/07/2023] Open

Abstract

Autophagy is a homeostatic, catabolic degradation process and cell fate essential regulatory mechanism. Protracted autophagy triggers cell death; its aberrant function is responsible for several malignancies. Panobinostat, a potent pan-deacetylase inhibitor, causes endoplasmic reticulum stress-induced cell death. The aim of this study was to investigate the role of autophagy in deacetylase inhibitor-triggered liver cancer cell death.HepG2 (p53wt) and Hep3B (p53 null) liver cancer cell lines were exposed to panobinostat. RT-qPCR and western blot confirmed autophagic factor modulation. Immuno-fluorescence, -precipitation and -histochemistry as well as transmission electron microscopy verified autophagosome formation. The cytotoxicity of panobinostat and autophagy modulators was detected using a real time cell viability assay.Panobinostat induced autophagy-related factor expression and aggregation. Map1LC3B and Beclin1 were significantly over-expressed in HepG2 xenografts in nude mice treated with panobinostat for 4 weeks. Subcellular distribution of Beclin1 increased with the appearance of autophagosomes-like aggregates. Cytosolic loss of p53, in HepG2, and p73, in Hep3B cells, and a corresponding gain of their nuclear level, together with modulation of DRAM1, were observed. Autophagosome aggregation was visible after 6 h of treatment. Treatment of cells stably expressing GFP-RFPtag Map1LC3B resulted in aggregation and a fluorescence switch, thus confirming autophagosome formation and maturation. Tamoxifen, an inducer of autophagy, caused only a block in cell proliferation; but in combination with panobinostat it resulted in cell death.Autophagy triggers cell demise in liver cancer. Its modulation by the combination of tamoxifen and panobinostat could be a new option for palliative treatment of hepatocellular carcinoma.

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He S, Zhao Z, Yang Y, O'Connell D, Zhang X, Oh S, Ma B, Lee JH, Zhang T, Varghese B, Yip J, Dolatshahi Pirooz S, Li M, Zhang Y, Li GM, Ellen Martin S, Machida K, Liang C. Truncating mutation in the autophagy gene UVRAG confers oncogenic properties and chemosensitivity in colorectal cancers. Nat Commun 2015;6:7839. [PMID: 26234763 PMCID: PMC4526116 DOI: 10.1038/ncomms8839] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Accepted: 06/17/2015] [Indexed: 12/19/2022] Open

Affiliation(s)

Shanshan He Department of Molecular Microbiology and Immunology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Zhen Zhao Department of Molecular Microbiology and Immunology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Yongfei Yang Department of Molecular Microbiology and Immunology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Douglas O'Connell Department of Molecular Microbiology and Immunology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Xiaowei Zhang Department of Molecular Microbiology and Immunology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Soohwan Oh Department of Molecular Microbiology and Immunology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Binyun Ma Department of Molecular Microbiology and Immunology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Joo-Hyung Lee Department of Molecular Microbiology and Immunology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Tian Zhang Department of Molecular Microbiology and Immunology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Bino Varghese Department of Radiology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Janae Yip Department of Molecular Microbiology and Immunology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Sara Dolatshahi Pirooz Department of Molecular Microbiology and Immunology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Ming Li Key Laboratory of Carcinogenesis and Translational Research, Department of Colorectal Surgery, Peking University Cancer Hospital &Institute, Beijing 100142, China
Yong Zhang Department of Surgical Oncology, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China
Guo-Min Li Graduate Center for Toxicology, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY 40506, USA
Sue Ellen Martin Department of Pathology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Keigo Machida Department of Molecular Microbiology and Immunology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA
Chengyu Liang Department of Molecular Microbiology and Immunology, Keck Medical School, University of Southern California, Los Angeles, California 90033, USA

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Hou L, Li Y, Song H, Zhang Z, Sun Y, Zhang X, Wu K. Protective Macroautophagy Is Involved in Vitamin E Succinate Effects on Human Gastric Carcinoma Cell Line SGC-7901 by Inhibiting mTOR Axis Phosphorylation. PLoS One 2015;10:e0132829. [PMID: 26168048 PMCID: PMC4500415 DOI: 10.1371/journal.pone.0132829] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Accepted: 06/19/2015] [Indexed: 12/26/2022] Open

Abstract

Vitamin E succinate (VES), a potential cancer therapeutic agent, potently induces apoptosis and inhibits the growth of various cancer cells. Autophagy has been supposed to promote cancer cell survival or trigger cell death, depending on particular cancer types and tumor microenvironments. The role of autophagy in the growth suppressive effect of VES on gastric cancer cell is basically unknown. We aimed to determine whether and how autophagy affected the VES-induced inhibition of SGC-7901 human gastric carcinoma cell growth. SGC-7901 cells were treated with VES or pre-treated with autophagy inhibitor, chloroquine (CQ) and 3-methyladenine (3-MA). Electron microscopy, fluorescence microscopy and Western blot were used to study whether VES induced autophagy reaction in SGC-7901 cells. Western blot evaluated the activities of the mammalian target of rapamycin (mTOR) axis. Then we used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry to detect the level of cell viability and apoptosis. Collectively, our data indeed strongly support our hypothesis that VES treatment produced cytological variations that depict autophagy, increased the amount of intracellular green fluorescent protein—microtubule associated protein 1 light chain 3 (GFP-LC3) punctate fluorescence and the number of autophagic vacuoles. It altered the expression of endogenous autophagy marker LC3. VES activated the suppression of mTOR through inhibiting upstream regulators p38 MAPK and Akt. mTOR suppression consequently inhibited the activation of mTOR downstream targets p70S6K and 4E-BP-1. The activation of the upstream mTOR inhibitor AMPK had been up-regulated by VES. The results showed that pre-treatment SGC-7901 with autophagy inhibitors before VES treatment could increase the capacity of VES to reduce cell viability and to provoke apoptosis. In conclusion, VES-induced autophagy participates in SGC-7901 cell protection by inhibiting mTOR axis phosphorylation. Our findings not only strengthen our understanding of the roles of autophagy in cancer biology, but may also be useful for developing new treatments for gastric cancer patients.

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Tan Q, Wang H, Hu Y, Hu M, Li X, Aodengqimuge, Ma Y, Wei C, Song L. Src/STAT3-dependent heme oxygenase-1 induction mediates chemoresistance of breast cancer cells to doxorubicin by promoting autophagy. Cancer Sci 2015;106:1023-32. [PMID: 26041409 PMCID: PMC4556392 DOI: 10.1111/cas.12712] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Revised: 05/27/2015] [Accepted: 05/28/2015] [Indexed: 12/15/2022] Open

Liu X, Niu Y, Yuan H, Huang J, Fu L. AMPK binds to Sestrins and mediates the effect of exercise to increase insulin-sensitivity through autophagy. Metabolism 2015;64:658-65. [PMID: 25672217 DOI: 10.1016/j.metabol.2015.01.015] [Citation(s) in RCA: 83] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2014] [Revised: 01/05/2015] [Accepted: 01/25/2015] [Indexed: 01/14/2023]

The Tribbles 2 (TRB2) pseudokinase binds to ATP and autophosphorylates in a metal-independent manner. Biochem J 2015;467:47-62. [PMID: 25583260 DOI: 10.1042/bj20141441] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]

Shukla S, Patric IRP, Patil V, Shwetha SD, Hegde AS, Chandramouli BA, Arivazhagan A, Santosh V, Somasundaram K. Methylation silencing of ULK2, an autophagy gene, is essential for astrocyte transformation and tumor growth. J Biol Chem 2014;289:22306-18. [PMID: 24923441 DOI: 10.1074/jbc.m114.567032] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open

Wang Z, Han W, Sui X, Fang Y, Pan H. Autophagy: A novel therapeutic target for hepatocarcinoma (Review). Oncol Lett 2014;7:1345-1351. [PMID: 24765136 PMCID: PMC3997714 DOI: 10.3892/ol.2014.1916] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Accepted: 01/27/2014] [Indexed: 12/19/2022] Open

Lithium improves survival of PC12 pheochromocytoma cells in high-density cultures and after exposure to toxic compounds. Int J Cell Biol 2014;2014:135908. [PMID: 24563652 PMCID: PMC3915898 DOI: 10.1155/2014/135908] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Accepted: 11/20/2013] [Indexed: 01/24/2023] Open

Ricci A, Cherubini E, Scozzi D, Pietrangeli V, Tabbì L, Raffa S, Leone L, Visco V, Torrisi MR, Bruno P, Mancini R, Ciliberto G, Terzano C, Mariotta S. Decreased expression of autophagic beclin 1 protein in idiopathic pulmonary fibrosis fibroblasts. J Cell Physiol 2013;228:1516-24. [PMID: 23444126 DOI: 10.1002/jcp.24307] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2012] [Accepted: 12/04/2012] [Indexed: 11/06/2022]

Bhutia SK, Mukhopadhyay S, Sinha N, Das DN, Panda PK, Patra SK, Maiti TK, Mandal M, Dent P, Wang XY, Das SK, Sarkar D, Fisher PB. Autophagy: cancer's friend or foe? Adv Cancer Res 2013;118:61-95. [PMID: 23768510 DOI: 10.1016/b978-0-12-407173-5.00003-0] [Citation(s) in RCA: 166] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]

Lu SZ, Harrison-Findik DD. Autophagy and cancer. World J Biol Chem 2013;4:64-70. [PMID: 23977422 PMCID: PMC3746279 DOI: 10.4331/wjbc.v4.i3.64] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2013] [Revised: 07/13/2013] [Accepted: 07/19/2013] [Indexed: 02/05/2023] Open