Abstract
Background: Molecular pathogenesis of hepatocellular carcinoma is complex and implies a multistep process involving different genetic and epigenetic alterations, as well as altered molecular pathways. Among these features, oxidative stress and mitochondria dysfunction represent an important trigger to hepatocarcinogenesis regardless of underlying liver disease etiology. An important part of the actual cancer research is focused on the molecular mechanisms and the signaling pathways involved in the process of so called “mitochondrial malignancy”. Method: Aim of this review is to summarize the main molecular mechanisms and the pathological consequences of oxidative stress and mitochondrial dysfunction in liver cancer. Furthermore, an up-to-date insight in therapeutic implications of the aforementioned processes is consistently developed. A literature search was conducted using PubMed until October 2015, based on English language journals. Results: Mitochondrial dysfunction may dramatically alter cell growth and proliferation by means of several “retrograde” mitochondria-nucleus signaling pathways, all of which have been shown to play a significant role in hepatocarcinogenesis. Nuclear oncogenes and tumor suppressors alike regulate mitochondrial turnover and function in a thick cross-talk whose role is fundamental in human oncology. Conclusion: The current knowledge on the role of mitochondrial signaling and oxidative stress in hepatocarcinogenesis seems to support the use of antioxidant agents in hepatocarcinoma patients, for instance in the adjuvant setting after radical treatments where their favorable cost-effective and safety profile may enable long-terms therapies aimed at preventing tumor recurrence. Data from randomized-controlled trials are warranted in order to confirm these promising results.
Keywords: Mitochondria, HCC, Liver cancer, Kinases, ROS, Oxidative stress.
Current Pharmaceutical Design
Title:Mitochondrial Signaling and Hepatocellular Carcinoma: Molecular Mechanisms and Therapeutic Implications
Volume: 22 Issue: 18
Author(s): Antonio Facciorusso, Rosanna Villani, Francesco Bellanti, Domenica Mitarotonda, Gianluigi Vendemiale and Gaetano Serviddio
Affiliation:
Keywords: Mitochondria, HCC, Liver cancer, Kinases, ROS, Oxidative stress.
Abstract: Background: Molecular pathogenesis of hepatocellular carcinoma is complex and implies a multistep process involving different genetic and epigenetic alterations, as well as altered molecular pathways. Among these features, oxidative stress and mitochondria dysfunction represent an important trigger to hepatocarcinogenesis regardless of underlying liver disease etiology. An important part of the actual cancer research is focused on the molecular mechanisms and the signaling pathways involved in the process of so called “mitochondrial malignancy”. Method: Aim of this review is to summarize the main molecular mechanisms and the pathological consequences of oxidative stress and mitochondrial dysfunction in liver cancer. Furthermore, an up-to-date insight in therapeutic implications of the aforementioned processes is consistently developed. A literature search was conducted using PubMed until October 2015, based on English language journals. Results: Mitochondrial dysfunction may dramatically alter cell growth and proliferation by means of several “retrograde” mitochondria-nucleus signaling pathways, all of which have been shown to play a significant role in hepatocarcinogenesis. Nuclear oncogenes and tumor suppressors alike regulate mitochondrial turnover and function in a thick cross-talk whose role is fundamental in human oncology. Conclusion: The current knowledge on the role of mitochondrial signaling and oxidative stress in hepatocarcinogenesis seems to support the use of antioxidant agents in hepatocarcinoma patients, for instance in the adjuvant setting after radical treatments where their favorable cost-effective and safety profile may enable long-terms therapies aimed at preventing tumor recurrence. Data from randomized-controlled trials are warranted in order to confirm these promising results.
Export Options
About this article
Cite this article as:
Facciorusso Antonio, Villani Rosanna, Bellanti Francesco, Mitarotonda Domenica, Vendemiale Gianluigi and Serviddio Gaetano, Mitochondrial Signaling and Hepatocellular Carcinoma: Molecular Mechanisms and Therapeutic Implications, Current Pharmaceutical Design 2016; 22 (18) . https://dx.doi.org/10.2174/1381612822666160209153624
DOI https://dx.doi.org/10.2174/1381612822666160209153624 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Exosomes: A Promising Factor Involved in Cancer Hypoxic Microenvironments
Current Medicinal Chemistry Functionalized Nanocarriers for Enhanced Bioactive Delivery to Squamous Cell Carcinomas: Targeting Approaches and Related Biopharmaceutical Aspects
Current Pharmaceutical Design Editorial [Hot topic:Metal-Containing Drugs and Novel Coordination Complexes in Therapeutic Anticancer Applications – Part I (Guest Editor: Irena Kostova)]
Anti-Cancer Agents in Medicinal Chemistry SPECT-CT in Radiotherapy Planning, with Main Reference to Patients with Breast Cancer
Current Radiopharmaceuticals Recent Advancements in Nanotechnology for Oral Cancer: a Review
Current Drug Therapy Antifolate Inhibitors of Thymidylate Synthase as Anticancer Drugs
Mini-Reviews in Medicinal Chemistry Aromatherapy and the Central Nerve System (CNS): Therapeutic Mechanism and its Associated Genes
Current Drug Targets Use of Analogs of Peptide Hormones Conjugated to Cytotoxic Radicals for Chemotherapy Targeted to Receptors on Tumors
Current Drug Delivery Palifermin in theManagement of Mucositis in Hematological Malignancies: Current Evidences and Future Perspectives
Cardiovascular & Hematological Agents in Medicinal Chemistry The Molecular Mechanisms for the Antitumorigenic Effect of Curcumin
Current Medicinal Chemistry - Anti-Cancer Agents Butyrate and Colorectal Cancer: The Role of Butyrate Transport
Current Drug Metabolism Imaging Requirements for Personalized Medicine: The Oncologists Point of View
Current Pharmaceutical Design Hypoglycaemia and Cardiovascular Disease Risk in Patients with Diabetes
Current Pharmaceutical Design Chemotherapeutic Agents That Induce Mitochondrial Apoptosis
Current Cancer Drug Targets Trends in Biotechnological Drugs for Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Current Advances in Retroviral Gene Therapy
Current Gene Therapy Cellular Systems Biology Profiling Applied to Cellular Models of Disease
Combinatorial Chemistry & High Throughput Screening Current Molecularly Targeting Therapies in NSCLC and Melanoma
Anti-Cancer Agents in Medicinal Chemistry Exploiting Endogenous Cellular Process to Generate Quinone Methides In Vivo
Current Organic Chemistry Exploring the Management of Statin Intolerant Patients: 2016 and Beyond
Current Vascular Pharmacology