Abstract
Over-expressed in cancer cells, hexokinase II (HK II) forms a mitochondrial complex, which promotes cancer survival. 3- Bromopyruvic acid (3-BrPA) dissociates HK II from this complex, causing cell death, and thus, having an anti-tumor effect. The design of this study was to first analyze the expression of HK II in the hepatoma cell line, BEL-7402, then investigate the effects of 3-Br-PA on these cells, and finally, discuss its potential for clinical usage. HK II expression was detected in BEL-7402 cells by immunocytochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). In vitro treatment of cells with 3-BrPA significantly inhibited their growth, as evaluated by MTT assay and adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA). To analyze the in vivo function and safety of this drug, a tumor model was established by subcutaneously implanting hepatic cancer cells into nude mice. 3-BrPA treatment (50 mg/kg ip. daily, 6 days/week for three weeks) was effective in the animal model by attenuating tumor growth and causing tumor necrosis. Toxic signs were not observed. The acute toxicity study provided an LD50 of 191.7 mg/kg for 3-BrPA. Taken together, our in vitro and in vivo analyses suggest that 3-BrPA exerts anti-hepatoma effects, and may be an effective pharmacological agent for the treatment of hepatocellular carcinoma.
Keywords: Antitumor effect, 3-Bromopyruvic acid, hepatoma BEL-7402 cells, Hexokinase II.
Anti-Cancer Agents in Medicinal Chemistry
Title:3-Bromopyruvic Acid, A Hexokinase II Inhibitor, is an Effective Antitumor Agent on the Hepatoma Cells : in vitro and in vivo Findings
Volume: 14 Issue: 5
Author(s): Lei Gong, Yuhua Wei, Xin Yu, Jirun Peng and Xisheng Leng
Affiliation:
Keywords: Antitumor effect, 3-Bromopyruvic acid, hepatoma BEL-7402 cells, Hexokinase II.
Abstract: Over-expressed in cancer cells, hexokinase II (HK II) forms a mitochondrial complex, which promotes cancer survival. 3- Bromopyruvic acid (3-BrPA) dissociates HK II from this complex, causing cell death, and thus, having an anti-tumor effect. The design of this study was to first analyze the expression of HK II in the hepatoma cell line, BEL-7402, then investigate the effects of 3-Br-PA on these cells, and finally, discuss its potential for clinical usage. HK II expression was detected in BEL-7402 cells by immunocytochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). In vitro treatment of cells with 3-BrPA significantly inhibited their growth, as evaluated by MTT assay and adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA). To analyze the in vivo function and safety of this drug, a tumor model was established by subcutaneously implanting hepatic cancer cells into nude mice. 3-BrPA treatment (50 mg/kg ip. daily, 6 days/week for three weeks) was effective in the animal model by attenuating tumor growth and causing tumor necrosis. Toxic signs were not observed. The acute toxicity study provided an LD50 of 191.7 mg/kg for 3-BrPA. Taken together, our in vitro and in vivo analyses suggest that 3-BrPA exerts anti-hepatoma effects, and may be an effective pharmacological agent for the treatment of hepatocellular carcinoma.
Export Options
About this article
Cite this article as:
Gong Lei, Wei Yuhua, Yu Xin, Peng Jirun and Leng Xisheng, 3-Bromopyruvic Acid, A Hexokinase II Inhibitor, is an Effective Antitumor Agent on the Hepatoma Cells : in vitro and in vivo Findings, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (5) . https://dx.doi.org/10.2174/1871520614666140416105309
DOI https://dx.doi.org/10.2174/1871520614666140416105309 |
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
-
Targeting Cancer Stem Cells with Natural Products
Current Drug Targets Current Constructs and Targets in Clinical Development for Antibody- Based Cancer Therapy
Current Drug Targets Wogonin Induces Cell Cycle Arrest and Apoptosis of Hepatocellular Carcinoma Cells by Activating Hippo Signaling
Anti-Cancer Agents in Medicinal Chemistry Challenges in the Correct Assessment of a Case of Aggressive Thyroid Carcinoma with Synchronous Breast Cancer: A Case Report and Review of the Literature of Essential Role of Radiopharmaceuticals
Current Radiopharmaceuticals Impact of Liver Cancer Somatic Mutations on Protein Structures and Functions
Current Proteomics Ferroptosis Inducers for Prostate Cancer Therapy
Current Medicinal Chemistry Anticancer Effects of Ginsenoside Rh2: A Systematic Review
Current Molecular Pharmacology Opportunities and Challenges for Niosomes as Drug Delivery Systems
Current Drug Delivery Can Diabetes Heal?- From Observations to Perspectives
Current Diabetes Reviews The Anticancer Properties of Dietary Polyphenols and its Relation with Apoptosis
Current Pharmaceutical Design Application of dsRNA in Cancer Immunotherapy: Current Status and Future Trends
Anti-Cancer Agents in Medicinal Chemistry Advances in Drug Discovery against Neglected Tropical Diseases: Human African and American Trypanosomiasis
Current Medicinal Chemistry Role of Toxicogenomics in the Development of Safe, Efficacious and Novel Anti-microbial Therapies.
Infectious Disorders - Drug Targets Coordinated Expression of Pax-5 and FAK1 in Metastasis
Anti-Cancer Agents in Medicinal Chemistry Chemoprevention with Phytonutrients and Microalgae Products in Chronic Inflammation and Colon Cancer
Current Pharmaceutical Design The Emerging Role of Vascular Endothelial Growth Factor (VEGF) in Vascular Homeostasis: Lessons from Recent Trials with Anti-VEGF Drugs
Current Vascular Pharmacology Benzamide and Benzamidine Compounds as New Inhibitors of Urokinasetype Plasminogen Activators
Mini-Reviews in Medicinal Chemistry Interplay of β-Catenin with Xenobiotic-Sensing Receptors and its Role in Glutathione S-Transferase Expression
Current Drug Metabolism Phosphatidylinositol 3-kinase Signaling as a Therapeutic Target for Cervical Cancer
Current Cancer Drug Targets Recent Contributions of Elastin-Like Recombinamers to Biomedicine and Nanotechnology
Current Topics in Medicinal Chemistry