Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Mol Carcinog ; 57(9): 1156-1165, 2018 09.
Article in English | MEDLINE | ID: mdl-29697164

ABSTRACT

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer death in men and women in the United States. Anti-inflammatory blockade has been proven to be a promising avenue of colorectal cancer prevention. However, NSAIDs while effective in curbing CRC risk are too toxic for long-term use in cancer prevention. The Neem tree (Azadirachta indica) is rich in liminoid terpenoids, collectively known as azadiractoids and has been shown to have anti-inflammatory effects. To explore a role of neem in CRC, human colon cancer cell lines HCT116 and HT29 cells were treated with purified Super Critical Neem Extract (SCNE) or the neem liminoid, nimbolide. SCNE treatment resulted in a dose dependent inhibition of CRC cell proliferation and an increase in apoptosis. Treatment with SCNE and nimbolide decreased the expression of transcriptional factors, STAT3 and NF-κB which plays a major role in gene regulation of multiple cellular processes. Protein expression of COX1, IL-6, and TNF-α were decreased on treatment with SCNE in CRC cells. Western blots and Zymogram assays results revealed anti-invasive effect by decreased expression of MMP2 and MMP9 proteins in CRC cells. Overall, these data confirm a potential anti-cancer effect of SCNE, reducing cell proliferation, inflammation, migration, and invasion in human colon cancer cells. Confirming these indications, we found that treatment of mice bearing HT29 and HCT116 xenografted tumors exhibited striking inhibition of colon tumor growth. Clearly we must explore the effect of neem in preclinical animal models for anti-cancer therapy.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Azadirachta/chemistry , Colonic Neoplasms/drug therapy , Inflammation/drug therapy , Limonins/therapeutic use , Plant Extracts/therapeutic use , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Carbon Dioxide/chemistry , Cell Movement/drug effects , Cell Proliferation/drug effects , Colonic Neoplasms/immunology , Colonic Neoplasms/pathology , HCT116 Cells , HT29 Cells , Humans , Inflammation/immunology , Inflammation/pathology , Limonins/isolation & purification , Limonins/pharmacology , Mice , Neoplasm Invasiveness/immunology , Neoplasm Invasiveness/pathology , Neoplasm Invasiveness/prevention & control , Plant Extracts/isolation & purification , Plant Extracts/pharmacology
2.
BMC Immunol ; 15: 38, 2014 Nov 26.
Article in English | MEDLINE | ID: mdl-25424735

ABSTRACT

BACKGROUND: The Syrian golden hamster (Mesocricetus aureus) has been used as a model to study infections caused by a number of human pathogens. Studies of immunopathogenesis in hamster infection models are challenging because of the limited availability of reagents needed to define cellular and molecular determinants. RESULTS: We sequenced a hamster cDNA library and developed a first-generation custom cDNA microarray that included 5131 unique cDNAs enriched for immune response genes. We used this microarray to interrogate the hamster spleen response to Leishmania donovani, an intracellular protozoan that causes visceral leishmaniasis. The hamster model of visceral leishmaniasis is of particular interest because it recapitulates clinical and immunopathological features of human disease, including cachexia, massive splenomegaly, pancytopenia, immunosuppression, and ultimately death. In the microarray a differentially expressed transcript was identified as having at least a 2-fold change in expression between uninfected and infected groups and a False Discovery Rate of <5%. Following a relatively silent early phase of infection (at 7 and 14 days post-infection only 8 and 24 genes, respectively, were differentially expressed), there was dramatic upregulation of inflammatory and immune-related genes in the spleen (708 differentially expressed genes were evident at 28 days post-infection). The differentially expressed transcripts included genes involved in inflammation, immunity, and immune cell trafficking. Of particular interest there was concomitant upregulation of the IFN-γ and interleukin (IL)-4 signaling pathways, with increased expression of a battery of IFN-γ- and IL-4-responsive genes. The latter included genes characteristic of alternatively activated macrophages. CONCLUSIONS: Transcriptional profiling was accomplished in the Syrian golden hamster, for which a fully annotated genome is not available. In the hamster model of visceral leishmaniasis, a robust and functional IFN-γ response did not restrain parasite load and progression of disease. This supports the accumulating evidence that macrophages are ineffectively activated to kill the parasite. The concomitant expression of IL-4/IL-13 and their downstream target genes, some of which were characteristic of alternative macrophage activation, are likely to contribute to this. Further dissection of mechanisms that lead to polarization of macrophages toward a permissive state is needed to fully understand the pathogenesis of visceral leishmaniasis.


Subject(s)
Cytokines/genetics , Gene Expression Profiling , Gene Expression Regulation , Leishmaniasis, Visceral/genetics , Leishmaniasis, Visceral/immunology , Spleen/metabolism , Spleen/parasitology , Animals , Cluster Analysis , Cricetinae , Cytokines/metabolism , DNA, Complementary/genetics , Disease Progression , Expressed Sequence Tags , Gene Ontology , Humans , Interferon-gamma/metabolism , Leishmania donovani/immunology , Mesocricetus/immunology , Mesocricetus/parasitology , Molecular Sequence Annotation , Oligonucleotide Array Sequence Analysis , Principal Component Analysis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Signal Transduction/genetics , Spleen/pathology , Up-Regulation/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...