Abstract
Hyaluronan (HA) and hyaluronan synthases (HAS) have been implicated in cancer growth and progression. We previously have shown that HAS3 and HA mediate tumor growth in SW620 colon cancer cells, but the mechanism remains poorly understood. In addition, the effect of HAS3 inhibition on tumor growth with other cells lines has not been explored. We therefore hypothesized that inhibition of HAS3 in highly tumorigenic HCT116 colon cancer cells would decrease tumor growth and that the underlying mechanism would involve altering proliferation and/or apoptosis. HAS3 expression was inhibited by transfection with siRNA; a scrambled sequence served as a control. Stable transfectants were injected into the flanks of nude mice and tumor growth followed for 30 days. Proliferation and apoptosis were then assessed in the harvested tumors. Results were compared using the Students t-test and ANOVA where appropriate. siRNA transfection decreased HAS3 expression, protein production, and pericellular HA retention, and decreased in vivo tumor growth. Proliferation was unaffected in the HCT116 tumors, but increased slightly in the SW620 tumors. In contrast, HAS3 inhibition significantly increased apoptosis in all tumors. HAS3 inhibition decreases subcutaneous tumor growth by colon cancer cells and significantly increases apoptosis with less effect on proliferation. These data show that HAS3 and HA mediate colon cancer growth by inhibiting apoptosis.
Keywords: Colon carcinoma, hyaluronan, hyaluronan synthase, apoptosis proliferation, HCT116, SW620, siRNA, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Invitrogen, electrophoresis, Immunocytochemistry
Anti-Cancer Agents in Medicinal Chemistry
Title: Inhibition of Hyaluronan Synthase-3 Decreases Subcutaneous Colon Cancer Growth by Increasing Apoptosis
Volume: 11 Issue: 7
Author(s): Brian P. Teng, Melissa D. Heffler, Eric C. Lai, Ya-Li Zhao, Charles M. LeVea, Vita M. Golubovskaya and Kelli M. BullardDunn
Affiliation:
Keywords: Colon carcinoma, hyaluronan, hyaluronan synthase, apoptosis proliferation, HCT116, SW620, siRNA, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Invitrogen, electrophoresis, Immunocytochemistry
Abstract: Hyaluronan (HA) and hyaluronan synthases (HAS) have been implicated in cancer growth and progression. We previously have shown that HAS3 and HA mediate tumor growth in SW620 colon cancer cells, but the mechanism remains poorly understood. In addition, the effect of HAS3 inhibition on tumor growth with other cells lines has not been explored. We therefore hypothesized that inhibition of HAS3 in highly tumorigenic HCT116 colon cancer cells would decrease tumor growth and that the underlying mechanism would involve altering proliferation and/or apoptosis. HAS3 expression was inhibited by transfection with siRNA; a scrambled sequence served as a control. Stable transfectants were injected into the flanks of nude mice and tumor growth followed for 30 days. Proliferation and apoptosis were then assessed in the harvested tumors. Results were compared using the Students t-test and ANOVA where appropriate. siRNA transfection decreased HAS3 expression, protein production, and pericellular HA retention, and decreased in vivo tumor growth. Proliferation was unaffected in the HCT116 tumors, but increased slightly in the SW620 tumors. In contrast, HAS3 inhibition significantly increased apoptosis in all tumors. HAS3 inhibition decreases subcutaneous tumor growth by colon cancer cells and significantly increases apoptosis with less effect on proliferation. These data show that HAS3 and HA mediate colon cancer growth by inhibiting apoptosis.
Export Options
About this article
Cite this article as:
P. Teng Brian, D. Heffler Melissa, C. Lai Eric, Zhao Ya-Li, M. LeVea Charles, M. Golubovskaya Vita and M. BullardDunn Kelli, Inhibition of Hyaluronan Synthase-3 Decreases Subcutaneous Colon Cancer Growth by Increasing Apoptosis, Anti-Cancer Agents in Medicinal Chemistry 2011; 11 (7) . https://dx.doi.org/10.2174/187152011796817655
DOI https://dx.doi.org/10.2174/187152011796817655 |
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
-
A Review of the Use of Stents for Palliation of Esophageal and Lung Cancer
Current Cancer Therapy Reviews Irreversible Multitargeted ErbB Family Inhibitors for Therapy of Lung and Breast Cancer
Current Cancer Drug Targets Pharmacokinetics-Guided Dosing of 5-Fluorouracil for Precision Cancer Treatment: A Focus on Colorectal Carcinoma
Applied Clinical Research, Clinical Trials and Regulatory Affairs Immunonutrition in Surgical Patients
Current Drug Targets Possible Consequences of Blocking Transient Receptor Potential Vanilloid 1
Current Pharmaceutical Biotechnology Non-histone Methylation of SET7/9 and its Biological Functions
Recent Patents on Anti-Cancer Drug Discovery Significance of Metallothionein Expression in Liver Disease
Current Pharmaceutical Biotechnology Single Nucleotide Polymorphisms as the Efficient Prognostic Markers in Breast Cancer
Current Cancer Drug Targets β -Glucans and their Applications in Cancer Therapy: Focus on human studies
Anti-Cancer Agents in Medicinal Chemistry Bortezomib as the First Proteasome Inhibitor Anticancer Drug: Current Status and Future Perspectives
Current Cancer Drug Targets Review of PI3K/mTOR Inhibitors Entering Clinical Trials to Treat Triple Negative Breast Cancers
Recent Patents on Anti-Cancer Drug Discovery Lgr5 Contributes to Intestinal Metaplasia During Gastric Carcinogenesis: A Meta analysis
Anti-Cancer Agents in Medicinal Chemistry Metastasis-Inducing S100A4 Protein: Implication in Non-Malignant Human Pathologies
Current Molecular Medicine Cancer Stem Cell Model in Oral Squamous Cell Carcinoma
Current Stem Cell Research & Therapy An Expanding Appreciation of the Role Chemokine Receptors Play in Cancer Progression
Current Pharmaceutical Design Separation of Bioactive Peptides by Membrane Processes: Technologies and Devices
Recent Patents on Biotechnology Small Interfering RNA for Effective Cancer Therapies
Mini-Reviews in Medicinal Chemistry Recent Patents on Light Based Therapies: Photodynamic Therapy, Photothermal Therapy and Photoimmunotherapy
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery A New 4-phenyl-1,8-naphthyridine Derivative Affects Carcinoma Cell Proliferation by Impairing Cell Cycle Progression and Inducing Apoptosis
Anti-Cancer Agents in Medicinal Chemistry Chemical and Biological Approaches for Mycotoxin Control: A Review
Recent Patents on Food, Nutrition & Agriculture