Helicobacter pylori infection is strongly associated with primary gastric diseases, such as extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, diffuse large B-cell lymphoma (DLBCL) with histologic evidence of MALT origin, and gastric carcinoma. The cytotoxin-associated gene A (CagA) protein behaves as a bacterial oncoprotein, promoting tumorigenesis via dysregulation of the phosphatidylinositol 3-kinase/AKT pathway (PI3K/AKT). We investigated the molecular mechanisms of PI3K/AKT pathway dysregulation in H. pylori-induced MALT and DLBCL gastric lymphoma. Immunohistochemical assays for CagA, phospho(p)-S473-AKT, PTEN, SHIP, and cyclin A2 proteins were performed on samples from 23 patients with H. pylori-positive MALT lymphoma and 16 patients with H. pylori-positive gastric DLBCL. We showed that CagA localization is correlated with the activation of the AKT pathway in both MALT and DLBCL lymphoma cells. Interestingly, we found a close association between the loss of PTEN, the overexpression of cyclin A2, and the phosphorylation of AKT in gastric MALT and DLBCL tumor cells.
Background:
The lack of treatment options for patients with chemotherapy-resistant cancers
is pushing the field toward the development of new therapies. 1,2,4,5-tetrazine derivatives are a class of
heterocyclic compounds that exhibit a broad spectrum of antitumor activities.
Objective:
The purpose of this study was to assess the biological activity of four s-tetrazine derivatives
by substitution of two chloride atom of 3,6-dichloro-1,2,4,5-tetrazine with long hydrophobic side
chains.
Methods:
We analyzed the anti-proliferative effects of four s-tetrazine derivatives with MTT assay and
their pro-apoptotic effect with AV/ IP flow cytometry analysis and Hoechst 33342 staining.
Results:
We demonstrated that 3,6-dichloro-1,2,4,5-tetrazine (compound (1)) has a cytotoxic effect and
induces apoptosis.
Conclusion:
3,6-dichloro-1,2,4,5-tetrazine presents a new cytotoxic drug against metastatic breast cancer
cell line MDA-MB-231 in vitro.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.