Abstract
Genistein, a nontoxic flavonoid compound, has potent antitumor activity in various cancer cells. In the present study, we investigated whether genistein could be employed as a novel strategy to enhance the anti-tumor activity of gemcitabine using human osteosarcoma MNNG/HOS tumor model. In vitro, by MTT, electron microscopy, immunobloting and qRT-PCR assay, we found that the combination treatment of genistein and gemcitabine resulted in stronger growth inhibition and apoptosis induction through the downregulation of NF-κB activity and Akt activation in osteosarcoma cells. Moreover, the synergetic effects were observed when genistein was replaced by PI3K/Akt-pathway inhibitor (LY-294002) or NF-κB inhibitor (BAY11-7082). In vivo, the combination therapy augmented tumor growth inhibition through the down-regulation of NF-κB activity and Akt activation in xenografts. Taken together, these results provide in vitro and in vivo evidence that genistein abrogates gemcitabine-induced activation of NF-κB and increases the chemosensitization of osteosarcoma to gemcitabine. Combination therapy appears as a rational and novel approach for osteosarcoma treatment.
Keywords: Akt, Apoptosis, Gemcitabine, Genistein, NF-κB, Osteosarcoma, Immunoblotting, Electron Microscopy, Xenograft, Electrophoretic, Immunohistochemistry
Anti-Cancer Agents in Medicinal Chemistry
Title:Genistein Potentiates the Anti-cancer Effects of Gemcitabine in Human Osteosarcoma via the Downregulation of Akt and Nuclear Factor-κB Pathway
Volume: 12 Issue: 5
Author(s): Chengzhen Liang, Hao Li, Chengchun Shen, Jianbo Lai, Zhongli Shi, Bing Liu and Hui-min Tao
Affiliation:
Keywords: Akt, Apoptosis, Gemcitabine, Genistein, NF-κB, Osteosarcoma, Immunoblotting, Electron Microscopy, Xenograft, Electrophoretic, Immunohistochemistry
Abstract: Genistein, a nontoxic flavonoid compound, has potent antitumor activity in various cancer cells. In the present study, we investigated whether genistein could be employed as a novel strategy to enhance the anti-tumor activity of gemcitabine using human osteosarcoma MNNG/HOS tumor model. In vitro, by MTT, electron microscopy, immunobloting and qRT-PCR assay, we found that the combination treatment of genistein and gemcitabine resulted in stronger growth inhibition and apoptosis induction through the downregulation of NF-κB activity and Akt activation in osteosarcoma cells. Moreover, the synergetic effects were observed when genistein was replaced by PI3K/Akt-pathway inhibitor (LY-294002) or NF-κB inhibitor (BAY11-7082). In vivo, the combination therapy augmented tumor growth inhibition through the down-regulation of NF-κB activity and Akt activation in xenografts. Taken together, these results provide in vitro and in vivo evidence that genistein abrogates gemcitabine-induced activation of NF-κB and increases the chemosensitization of osteosarcoma to gemcitabine. Combination therapy appears as a rational and novel approach for osteosarcoma treatment.
Export Options
About this article
Cite this article as:
Liang Chengzhen, Li Hao, Shen Chengchun, Lai Jianbo, Shi Zhongli, Liu Bing and Tao Hui-min, Genistein Potentiates the Anti-cancer Effects of Gemcitabine in Human Osteosarcoma via the Downregulation of Akt and Nuclear Factor-κB Pathway, Anti-Cancer Agents in Medicinal Chemistry 2012; 12 (5) . https://dx.doi.org/10.2174/187152012800617867
DOI https://dx.doi.org/10.2174/187152012800617867 |
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
-
Pharmacokinetics and Pharmacodynamics of Oseltamivir in Neonates, Infants and Children
Infectious Disorders - Drug Targets Effects of Polysaccharides from Selenium-enriched Pyracantha fortuneana on Mice Liver Injury
Medicinal Chemistry Activation of CAR and PXR by Dietary, Environmental and Occupational Chemicals Alters Drug Metabolism, Intermediary Metabolism, and Cell Proliferation
Current Pharmacogenomics and Personalized Medicine Emerging Roles for Modulation of microRNA Signatures in Cancer Chemoprevention
Current Cancer Drug Targets Targeting Mitochondria in Fighting Cancer
Current Pharmaceutical Design Preventing and Treating Anthracycline-Related Cardiotoxicity in Survivors of Childhood Cancer
Current Cancer Therapy Reviews ANTI-ADHESION Evolves To a Promising Therapeutic Concept in Oncology
Current Medicinal Chemistry Preparation and Characterization of a Novel Recombinant Human Parathyroid Hormone (1 – 34) Analog (Gly1-Gln26-rhPTH(1-34)) with Enhanced Biological Activity
Protein & Peptide Letters Automatic Initialization of Level Set Methods in Discontinuity Regions of Liver in CT Scans
Current Medical Imaging MicroRNAs Implications in the Onset, Diagnosis, and Prognosis of Osteosarcoma
Current Molecular Medicine Dual Roles of Sulforaphane in Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Inhibition of Cdc42-Interacting Protein 4 (CIP4) Impairs Osteosarcoma Tumor Progression
Current Cancer Drug Targets Substrates for Improved Live-Cell Fluorescence Labeling of SNAP-tag
Current Pharmaceutical Design Targeting Ion Channels for New Strategies in Cancer Diagnosis and Therapy
Current Clinical Pharmacology Automated Radiosynthesis and Molecular Docking Studies of Coumarin- Triazole Hybrid with fluorine-18: A feasibility study
Current Radiopharmaceuticals Dysregulation of Lysyl Oxidases Expression in Diabetic Nephropathy and Renal Cell Carcinoma
Current Drug Targets New Approaches to the Modulation of the Cyclooxygenase-2 and 5-Lipoxygenase Pathways
Current Topics in Medicinal Chemistry Serum Amyloid A and Its Potential Physiological / Pathological Functions - an Overview of Patents
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery The Role of NF-κB Inhibitors in Cell Response to Radiation
Current Medicinal Chemistry Insulin-Like Growth Factor-I Molecular Pathways in Osteoblasts: Potential Targets for Pharmacological Manipulation
Current Molecular Pharmacology