Abstract
Purpose: Platelet extracts can stimulate cell growth and contribute to tumor biology. It was recently shown that they stimulate the growth of hepatocellular carcinoma (HCC) cells and decrease apoptosis. Doxorubicin is a commonly used HCC chemotherapy that increases apoptosis. We therefore examined the effects of platelet lysates (hPL) on doxorubicin-mediated HCC cell growth inhibition and apoptosis induction.
Methods: Three human HCC cell lines, PLC/PRF/5, Hep3B and HepG2 cells, were grown in culture and growth was measured by the MTT assay and apoptosis was measured using Muse Annexin V assay kit. Cells were also probed by Western blot.
Results: hPL decreased doxorubicin-mediated growth inhibition and apoptosis induction in all three cell lines. When doxorubicin and hPL were added at separate time intervals, protection by hPL was also observed. WB showed that hPL caused prolonged and increased levels of phospho-JNK and phospho-p38. Furthermore, a p38 inhibitor abrogated the modulating effects of hPL on both growth and apoptosis, indicating its importance in mediating hPL actions. WBs also showed that hPL decreased doxorubicin-induced markers of apoptosis.
Conclusions: hPL modulate the actions of the cancer chemotherapeutic agent, doxorubicin. Platelets are part of the complex microenvironmental milieu and their effects may contribute to a modulation of chemotherapy actions. Conversely, drugs that alter platelet levels or degranulation could potentially augment doxorubicin actions on HCC cells.
Keywords: Apoptosis, autophagy, cell growth, doxorubicin, HCC, platelets.
Anti-Cancer Agents in Medicinal Chemistry
Title:Modulation of Doxorubicin Mediated Growth Inhibition of Hepatocellular Carcinoma Cells by Platelet Lysates
Volume: 14 Issue: 8
Author(s): Maria Grazia Refolo, Rosalba D'Alessandro, Catia Lippolis, Caterina Messa, Nicola Carella, Aldo Cavallini and Brian I. Carr
Affiliation:
Keywords: Apoptosis, autophagy, cell growth, doxorubicin, HCC, platelets.
Abstract: Purpose: Platelet extracts can stimulate cell growth and contribute to tumor biology. It was recently shown that they stimulate the growth of hepatocellular carcinoma (HCC) cells and decrease apoptosis. Doxorubicin is a commonly used HCC chemotherapy that increases apoptosis. We therefore examined the effects of platelet lysates (hPL) on doxorubicin-mediated HCC cell growth inhibition and apoptosis induction.
Methods: Three human HCC cell lines, PLC/PRF/5, Hep3B and HepG2 cells, were grown in culture and growth was measured by the MTT assay and apoptosis was measured using Muse Annexin V assay kit. Cells were also probed by Western blot.
Results: hPL decreased doxorubicin-mediated growth inhibition and apoptosis induction in all three cell lines. When doxorubicin and hPL were added at separate time intervals, protection by hPL was also observed. WB showed that hPL caused prolonged and increased levels of phospho-JNK and phospho-p38. Furthermore, a p38 inhibitor abrogated the modulating effects of hPL on both growth and apoptosis, indicating its importance in mediating hPL actions. WBs also showed that hPL decreased doxorubicin-induced markers of apoptosis.
Conclusions: hPL modulate the actions of the cancer chemotherapeutic agent, doxorubicin. Platelets are part of the complex microenvironmental milieu and their effects may contribute to a modulation of chemotherapy actions. Conversely, drugs that alter platelet levels or degranulation could potentially augment doxorubicin actions on HCC cells.
Export Options
About this article
Cite this article as:
Refolo Grazia Maria, D'Alessandro Rosalba, Lippolis Catia, Messa Caterina, Carella Nicola, Cavallini Aldo and Carr I. Brian, Modulation of Doxorubicin Mediated Growth Inhibition of Hepatocellular Carcinoma Cells by Platelet Lysates, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (8) . https://dx.doi.org/10.2174/1871520614666140604120226
DOI https://dx.doi.org/10.2174/1871520614666140604120226 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
Related Articles
-
Glucose Oncometabolism of Esophageal Cancer
Anti-Cancer Agents in Medicinal Chemistry Flavonoids in Atherosclerosis: An Overview of Their Mechanisms of Action
Current Medicinal Chemistry Pleiotropic Effects of PPARγ Agonist on Hemostatic Activation in Type 2 Diabetes Mellitus
Current Vascular Pharmacology Phenolic Compounds: the Role of Redox Regulation in Neurodegenerative Disease and Cancer
Mini-Reviews in Medicinal Chemistry Idiopathic Transverse Myelitis and Neuromyelitis Optica: Clinical Profiles,Pathophysiology and Therapeutic Choices
Current Neuropharmacology Cranberry for Urinary Tract Infection: From Bench to Bedside
Current Topics in Medicinal Chemistry Vaccination Against Angiogenesis-Associated Antigens: A Novel Cancer Immunotherapy Strategy
Current Molecular Medicine 3-Substituted Isocoumarins as Thymidine Phosphorylase Inhibitors
Letters in Drug Design & Discovery Optimising the Azeotropic Drying of 18F-Fluorine Wayto Improve the 18F-Fluorocholine Radiochemical Yield
Current Radiopharmaceuticals Biosystems Engineering of Prokaryotes with Tumor-Killing Capacities
Current Pharmaceutical Design The Therapeutic Potential of ADAM15
Current Pharmaceutical Design Intestinal Immunomodulation. Role of Regulative Peptides and Promising Pharmacological Activities
Current Pharmaceutical Design Specialisation of the Tropomyosin Composition of Actin Filaments Provides New Potential Targets for Chemotherapy
Current Cancer Drug Targets Diabetes-induced Epigenetic Signature in Vascular Cells
Endocrine, Metabolic & Immune Disorders - Drug Targets The Re-Emergence of Aerosol Gene Delivery: A Viable Approach to Lung Cancer Therapy
Current Cancer Drug Targets Natural and Synthetic Retinoids in Prostate Cancer
Current Pharmaceutical Design Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder
Current Medicinal Chemistry Identifying and Validating Oncology Therapeutic Targets in the Post- Genomics Era
Current Genomics Mitosis-Targeting Natural Products for Cancer Prevention and Therapy
Current Drug Targets Functional Genomics of the Oxidative Stress Pathway
Current Hypertension Reviews