Abstract
Hepatocellular carcinoma (HCC) is one of the prominent forms of cancer in developed countries. Globally, the incidence of HCC is well correlated with fatty liver disease and cirrhosis; the underlying chronic inflammation and lipotoxicity are thought to drive the process of HCC. Several biochemical cycles and molecular pathways are associated. The review aims to summarize the role of PI3K/Akt signaling and its downstream effectors in the development of HCC and its progression. Further, the emphasis has been given to the role of natural inhibitors of the PI3K/Akt pathway in HCC prevention, which are under various levels of drug discovery. The required literature were collected from PubMed/Medline databases, as well as Scopus or Web of science. It is evident that various signaling pathways activated by growth factors together with detoxification machinery and biochemical cycles converge to the PI3K/Akt signaling. The pathway plays a key role in the carcinogenesis, metastasis and drug resistance events of HCC cells and provides the growth and survival advantage. Natural products belonging to various classes such as terpenoids, flavonoids, saponins and stilbenoids are proven inhibitors of PI3K signaling and also found to inhibit HCC progression. PI3K/mTOR pathway inhibitors, especially the different phytochemicals, emerged as promising as anti-HCC agents. These molecules are shown to interfere with the PI3K signaling at various stages and therefore the PI3K targeted drugs may be a future for the chemotherapeutic arena.
Keywords: Hepatocellular carcinoma, PI3K/Akt pathway, natural products, metastasis, drug resistance, apoptosis.
Current Molecular Pharmacology
Title:Natural Products as PI3K/ Akt Inhibitors: Implications in Preventing Hepatocellular Carcinoma
Volume: 14
Author(s): Arunaksharan Narayanankutty*
Affiliation:
- Division of Cell and Molecular Biology, PG and Research Department of Zoology, St. Joseph's College (Autonomous), Devagiri, Calicut, Kerala,India
Keywords: Hepatocellular carcinoma, PI3K/Akt pathway, natural products, metastasis, drug resistance, apoptosis.
Abstract: Hepatocellular carcinoma (HCC) is one of the prominent forms of cancer in developed countries. Globally, the incidence of HCC is well correlated with fatty liver disease and cirrhosis; the underlying chronic inflammation and lipotoxicity are thought to drive the process of HCC. Several biochemical cycles and molecular pathways are associated. The review aims to summarize the role of PI3K/Akt signaling and its downstream effectors in the development of HCC and its progression. Further, the emphasis has been given to the role of natural inhibitors of the PI3K/Akt pathway in HCC prevention, which are under various levels of drug discovery. The required literature were collected from PubMed/Medline databases, as well as Scopus or Web of science. It is evident that various signaling pathways activated by growth factors together with detoxification machinery and biochemical cycles converge to the PI3K/Akt signaling. The pathway plays a key role in the carcinogenesis, metastasis and drug resistance events of HCC cells and provides the growth and survival advantage. Natural products belonging to various classes such as terpenoids, flavonoids, saponins and stilbenoids are proven inhibitors of PI3K signaling and also found to inhibit HCC progression. PI3K/mTOR pathway inhibitors, especially the different phytochemicals, emerged as promising as anti-HCC agents. These molecules are shown to interfere with the PI3K signaling at various stages and therefore the PI3K targeted drugs may be a future for the chemotherapeutic arena.
Export Options
About this article
Cite this article as:
Narayanankutty Arunaksharan *, Natural Products as PI3K/ Akt Inhibitors: Implications in Preventing Hepatocellular Carcinoma, Current Molecular Pharmacology 2021; 14 (5) . https://dx.doi.org/10.2174/1874467214666210120152657
DOI https://dx.doi.org/10.2174/1874467214666210120152657 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |
Call for Papers in Thematic Issues
Common mechanisms underpinning neurodevelopmental disorders and psychiatric diseases
A growing number of large-scale epidemiologic studies has strongly suggested that common mechanisms may be shared by aberrant brain development and psychiatric disorders. There is now an appreciation of synergic roles of genetic variants and environmental stress which profoundly affect the genome integrity and reshape brain development. This can lead ...read more
Pharmacology and Toxicology of Plant Bioactive Compounds
The thematic issue "Pharmacology and Toxicology of Plant Bioactive Compounds" aims to explore the multifaceted aspects of bioactive compounds derived from plants, delving into their pharmacological properties and potential toxicological implications. This issue will encompass a wide array of research, including investigations into the therapeutic benefits of plant-derived compounds, such ...read more
![](/images/wayfinder.jpg)
- 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
Related Articles
-
Organoselenium Compounds in Cancer Chemoprevention
Mini-Reviews in Medicinal Chemistry DNA Microarrays: Perspectives for Hypothesis-Driven Transcriptome Research and for Clinical Applications
Current Genomics Melanoma and Epigenetic Treatment: Past and Future
Anti-Cancer Agents in Medicinal Chemistry Improving the Efficacy of Anticancer Drugs via Encapsulation and Acoustic Release
Current Topics in Medicinal Chemistry Combination of DC Vaccine and Conventional Chemotherapeutics
Anti-Cancer Agents in Medicinal Chemistry Cyclodextrin Based Nanosponges: A Multidimensional Drug Delivery System and its Biomedical Applications
Current Drug Delivery Reconsideration of Japanese Traditional Herbal Medicine: New Field of Research and Clinical Medicine
Mini-Reviews in Medicinal Chemistry Toll-Like Receptors and their Role in Hematologic Malignancies
Current Molecular Medicine Anticancer Drug Sensitivity Testing, a Historical Review and Future Perspectives
Current Drug Therapy Ghrelin: A Molecular Target for Weight Regulation, Glucose and Lipid Metabolism
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Natural Bio-Drugs as Matrix Metalloproteinase Inhibitors: New Perspectives on the Horizon?
Recent Patents on Anti-Cancer Drug Discovery Manganese Superoxide Dismutase (Sod2) and Redox-Control of Signaling Events That Drive Metastasis
Anti-Cancer Agents in Medicinal Chemistry Combined Treatment with Octreotide, Galanin and Serotonin in Gastrointestinal Malignancies
Letters in Drug Design & Discovery Mining the Dark Matter of the Cancer Proteome for Novel Biomarkers
Current Cancer Therapy Reviews Chemokines and their Receptors in Gut Homeostasis and Disease
Current Immunology Reviews (Discontinued) [6]-gingerol as a Cancer Chemopreventive Agent: A Review of Its Activity on Different Steps of the Metastatic Process
Mini-Reviews in Medicinal Chemistry Benzimidazole Derivatives as Kinase Inhibitors
Current Medicinal Chemistry A Systematic Review of Genes Involved in the Inverse Resistance Relationship Between Cisplatin and Paclitaxel Chemotherapy: Role of BRCA1
Current Cancer Drug Targets The Role of Oxaliplatin-Based Versus Cisplatin-Based Regimens in Advanced Gastric Cancer: A Systematic Review and Pooled Analysis of the Chinese Literature
Current Cancer Therapy Reviews Effects of Olive Oil on TNF-α and IL-6 in Humans: Implication in Obesity and Frailty
Endocrine, Metabolic & Immune Disorders - Drug Targets