Abstract
Cellular and molecular mechanisms related to lung cancer have been extensively studied in recent years, but the availability of effective treatments is still scarce. Hecogenin acetate, a natural saponin presenting a wide spectrum of reported pharmacological activities, has been previously evaluated for its anticancer/antiproliferative activity in some in vivo and in vitro models. Here, we investigated the effects of hecogenin acetate in a human lung cancer cell line. A549 non-small lung cancer cells were exposed to different concentrations of hecogenin acetate and reactive species production, ERK1/2 activation, matrix metalloproteinase expression, cell cycle arrest and cell senescence parameters were evaluated. Hecogenin acetate significantly inhibited increase in intracellular reactive species production induced by H2O2. In addition, hecogenin acetate blocked ERK1/2 phosphorylation and inhibited the increase in MMP-2 caused by H2O2. Treatment with hecogenin acetate induced G0/G1-phase arrest at two concentrations (75 and 100 µM, 74% and 84.3% respectively), and increased the staining of senescence-associated β -galactosidase positive cells. These data indicate that hecogenin acetate is able to exert anti-cancer effects by modulating reactive species production, inducing cell cycle arrest and senescence and also modulating ERK1/2 phosphorylation and MMP-2 production.
Keywords: Cell cycle, ERK1/2, hecogenin acetate, non-small cell lung cancer, senescence.
Anti-Cancer Agents in Medicinal Chemistry
Title:Hecogenin Acetate Inhibits Reactive Oxygen Species Production and Induces Cell Cycle Arrest and Senescence in the A549 Human Lung Cancer Cell Line
Volume: 14 Issue: 8
Author(s): Juciano Gasparotto, Nauana Somensi, Alice Kunzler, Carolina Saibro Girardi, Matheus Augusto de Bittencourt Pasquali, Vitor Miranda Ramos, Andre Simoes-Pires, Lucindo Jose Quintans-Junior, Alexsandro Branco, Jose Claudio Fonseca Moreira and Daniel Pens Gelain
Affiliation:
Keywords: Cell cycle, ERK1/2, hecogenin acetate, non-small cell lung cancer, senescence.
Abstract: Cellular and molecular mechanisms related to lung cancer have been extensively studied in recent years, but the availability of effective treatments is still scarce. Hecogenin acetate, a natural saponin presenting a wide spectrum of reported pharmacological activities, has been previously evaluated for its anticancer/antiproliferative activity in some in vivo and in vitro models. Here, we investigated the effects of hecogenin acetate in a human lung cancer cell line. A549 non-small lung cancer cells were exposed to different concentrations of hecogenin acetate and reactive species production, ERK1/2 activation, matrix metalloproteinase expression, cell cycle arrest and cell senescence parameters were evaluated. Hecogenin acetate significantly inhibited increase in intracellular reactive species production induced by H2O2. In addition, hecogenin acetate blocked ERK1/2 phosphorylation and inhibited the increase in MMP-2 caused by H2O2. Treatment with hecogenin acetate induced G0/G1-phase arrest at two concentrations (75 and 100 µM, 74% and 84.3% respectively), and increased the staining of senescence-associated β -galactosidase positive cells. These data indicate that hecogenin acetate is able to exert anti-cancer effects by modulating reactive species production, inducing cell cycle arrest and senescence and also modulating ERK1/2 phosphorylation and MMP-2 production.
Export Options
About this article
Cite this article as:
Gasparotto Juciano, Somensi Nauana, Kunzler Alice, Girardi Saibro Carolina, Pasquali Augusto de Bittencourt Matheus, Ramos Miranda Vitor, Simoes-Pires Andre, Quintans-Junior Jose Lucindo, Branco Alexsandro, Moreira Claudio Fonseca Jose and Gelain Pens Daniel, Hecogenin Acetate Inhibits Reactive Oxygen Species Production and Induces Cell Cycle Arrest and Senescence in the A549 Human Lung Cancer Cell Line, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (8) . https://dx.doi.org/10.2174/1871520614666140408151751
DOI https://dx.doi.org/10.2174/1871520614666140408151751 |
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
-
Modulation of Cellular Response to Anticancer Treatment by Caffeine: Inhibition of Cell Cycle Checkpoints, DNA Repair and More
Current Pharmaceutical Biotechnology ABC Transporters and Drug Resistance in Patients with Epilepsy
Current Pharmaceutical Design Nanotechnological Strategies to Improve Water Solubility of Commercially Available Drugs
Current Nanomedicine Antitumor Effect of Butanoylated Heparin with Low Anticoagulant Activity on Lung Cancer Growth in Mice and Rats
Current Cancer Drug Targets Computer-aided Diagnosis of Lung Cancer in Computed Tomography Scans: A Review
Current Medical Imaging The Cyclin-Dependent Kinase Inhibitor p21CDKN1A as a Target of Anti-Cancer Drugs
Current Cancer Drug Targets The Ubiquitin+Proteasome Protein Degradation Pathway as a Therapeutic Strategy in the Treatment of Solid Tumor Malignancies
Anti-Cancer Agents in Medicinal Chemistry Galanthus nivalis Agglutinin (GNA)-Related Lectins: Traditional Proteins, Burgeoning Drugs?
Current Chemical Biology Measurement of CYP1A2 Activity: A Focus on Caffeine as a Probe
Current Drug Metabolism Thioredoxin System Modulation by Plant and Fungal Secondary Metabolites
Current Medicinal Chemistry 9-Hydroxyellipticine and Derivatives as Chemotherapy Agents
Mini-Reviews in Medicinal Chemistry Sphingolipids as Emerging Drug Targets: Therapeutic Applications of Ceramide Analogs
Drug Design Reviews - Online (Discontinued) Strategies to Convert PACAP from a Hypophysiotropic Neurohormone Into a Neuroprotective Drug
Current Pharmaceutical Design Phytochemicals and Antioxidants: An Evaluation in Understanding the Human Lifeline
Current Nutrition & Food Science Cancer Drug Development Using Glucose Metabolism Radiopharmaceuticals
Current Pharmaceutical Design Perspectives in Biomolecular Therapeutic Intervention in Cancer: From the Early to the New Strategies With Type I Interferons
Current Medicinal Chemistry Targeting Apoptosis Resistance in Rhabdomyosarcoma
Current Cancer Drug Targets A Review of HPLC Methods Used for Determining the Presence of Meloxicam
Current Pharmaceutical Analysis Absorption, Pharmacokinetics and Disposition of Biodegradable Nanoscale Preparations
Current Drug Metabolism PET Molecular Imaging of Hypoxia in Ischemic Stroke: An Update
Current Vascular Pharmacology