Lipopolysaccharide supports maintaining the stemness of CD133(+) hepatoma cells through activation of the NF-kappaB/HIF-1alpha pathway.
*Cancer stem cells; *Lipopolysaccharide; *Plasticity; *Stemness maintenance; *Tumor microenvironment; AC133 Antigen/genetics/*metabolism; alpha Subunit/genetics/*metabolism; Animals; Antineoplastic Agents – Pharmacodynamics; Antineoplastic Agents/pharmacology; Body Weights and Measures; Carcinoma; Cell Line; Cell Movement – Drug Effects; Cell Movement/drug effects; Cell Physiology; Cell Physiology – Drug Effects; Cell Proliferation/drug effects; Drug Resistance; Gene Expression Regulation; Genes; Genetic Techniques; Hepatocellular; Hepatocellular – Drug Therapy; Hepatocellular – Metabolism; Hepatocellular – Pathology; Hepatocellular/drug therapy/genetics/*metabolism/pathology; Humans; Hypoxia-Inducible Factor 1; Inbred BALB C; Lipopolysaccharides – Pharmacodynamics; Lipopolysaccharides/*pharmacology; Liver Neoplasms; Liver Neoplasms – Drug Therapy; Liver Neoplasms – Metabolism; Liver Neoplasms – Pathology; Liver Neoplasms/drug therapy/genetics/*metabolism/pathology; Male; Mice; Neoplasm; Neoplasm Invasiveness; Neoplastic; Neoplastic Stem Cells/*drug effects/metabolism/pathology; NF-kappa B – Metabolism; NF-kappa B/*metabolism; Nude; Phenotype; Proteins; Proteins – Metabolism; RNA Interference; Signal Transduction – Drug Effects; Signal Transduction/drug effects; Stem Cells – Drug Effects; Stem Cells – Metabolism; Stem Cells – Pathology; Time Factors; Transfection; Tumor Burden; Tumor Microenvironment
Due to the existence of cancer stem cells (CSCs), persistence and relapse of human hepatocellular carcinoma (HCC) are common after treatment with existing anti-cancer therapies. Emerging evidence indicates that lipopolysaccharide (LPS) plays a crucial role in aggravating HCC, but information about the effect of LPS on CSCs of HCC remains scant. Here, we report that the stemness of CD133(+) CSCs sorted from the human HCC cell line Huh7 was maintained well when cells were cultured with LPS. The reduction of CD133 expression was much lesser in cultured CSCs in the presence of LPS. In response to LPS stimulation, CSCs showed an increase in their activity of clonogenesis and tumorigenesis. LPS also supported maintaining CSC abilities of migration, invasion, and chemo-resistance. Treatment with HIF-1alpha-specific siRNA significantly reduced CD133 expression by CSCs at both mRNA and protein levels. Further, the expression of HIF-1alpha and CD133 was reduced in LPS-stimulated CSCs when the NF-kappaB inhibitor was added to the cell culture. HIF-1alpha-specific siRNA also effectively counteracted the effect of LPS on maintaining CSC abilities of migration and invasion. These data indicate that LPS, an important mediator in the liver tumor microenvironment, supports the maintenance of CSC stemness through signaling of the NF-kappaB/HIF-1alpha pathway. Our current study highlights LPS as a potential target for developing new therapeutic approaches to eliminate CSCs during the treatment of HCC.
Lai Fo-Bao; Liu Wen-Ting; Jing Ying-Ying; Yu Guo-Feng; Han Zhi-Peng; Yang Xue; Zeng Jian-Xing; Zhang Hang-Jie; Shi Rong-Yu; Li Xiao-Yong; Pan Xiao-Rong; Li Rong; Zhao Qiu-Dong; Wu Meng-Chao; Zhang Ping; Liu Jing-Feng; Wei Li-Xin
Cancer letters
2016
2016-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.canlet.2016.05.014" target="_blank" rel="noreferrer noopener">10.1016/j.canlet.2016.05.014</a>
Potential Benefits of Edible Berries in the Management of Aerodigestive and Gastrointestinal Tract Cancers: Preclinical and Clinical Evidence.
aerodigestive and gastrointestinal tract; Animal; Animal Studies; Animals; Anthocyanins/analysis/pharmacology; Anticarcinogenic Agents/*analysis/pharmacology; Antineoplastic Agents – Analysis; Antineoplastic Agents – Pharmacodynamics; Benzopyrans – Analysis; Benzopyrans – Pharmacodynamics; Berry; Biological; cancer; chemoprevention; Clinical Trials; Clinical Trials as Topic; Digestion – Drug Effects; Digestion/drug effects; Disease Models; Ellagic Acid/analysis/pharmacology; Fruit; Fruit/*chemistry; Gastrointestinal Neoplasms – Prevention and Control; Gastrointestinal Neoplasms/*prevention & control; Human; Humans; Models; Phytochemicals – Analysis; Phytochemicals – Pharmacodynamics; Phytochemicals/analysis/pharmacology; Plant Extracts – Analysis; Plant Extracts – Pharmacodynamics; Plant Extracts/*analysis/pharmacology; Polyphenols – Analysis; Polyphenols – Pharmacodynamics; Polyphenols/analysis/pharmacology; treatment
Epidemiological reports as well as experimental studies have demonstrated the significant health benefits provided by regular berry consumption. Berries possess both prophylactic and therapeutic potential against several chronic illnesses, such as cardiovascular, neurodegenerative, and neoplastic diseases. Berries owe their health benefits to phytoconstituents, such as polyphenolic anthocyanins, ellagic acid, and a diverse array of phytochemicals bestowed with potent antioxidant and anti-inflammatory effects as well as the ability to engage a multitude of signaling pathways. This review highlights the principal chemical constituents present in berries and their primary molecular targets. The article presents and critically analyzes the chemopreventive and therapeutic potential of berry extracts, fractions, and bioactive components on various cancers of the gastrointestinal tract (GIT), including esophageal, stomach, intestinal, and colorectal cancers as well as cancers of the upper aerodigestive tract, such as oral cancer. The current status of clinical studies evaluating berry products in several aforementioned cancers is presented. Various emerging issues including dose-ranging and dosage forms, the role of synergy and the usage of combination therapy as well as other relevant areas essential for the development of berry phytoconstituents as mainstream chemopreventive and therapeutic agents against aerodigestive and GIT cancers are critically discussed.
Bishayee Anupam; Haskell Yennie; Do Chau; Siveen Kodappully Sivaraman; Mohandas Nima; Sethi Gautam; Stoner Gary D
Critical reviews in food science and nutrition
2016
2016-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1080/10408398.2014.982243" target="_blank" rel="noreferrer noopener">10.1080/10408398.2014.982243</a>