Oleanolic acid initiates apoptosis in non-small cell lung cancer cell lines and reduces metastasis of a B16F10 melanoma model in vivo.

BACKGROUND: Drug resistance, a process mediated by multiple mechanisms, is a critical determinant for treating lung cancer. The aim of this study is to determine if oleanolic acid (OA), a pentacyclic triterpene present in several plants, is able to circumvent the mechanisms of drug resistance present in non-small cell lung cancer (NSCLC) cell lines and to induce their death. PRINCIPAL FINDINGS: OA decreased the cell viability of the NSCLC cell lines A459 and H460 despite the presence of active, multidrug-resistant (MDR) MRP1/ABCC1 proteins and the anti-apoptotic proteins Bcl-2 and survivin. These effects are due to apoptosis, as evidenced by the capacity of OA to induce fragmentation of DNA and activate caspase 3. Induction of NSCLC cell death by OA cannot be explained by inhibition of the MDR proteins, since treatment with triterpene had little or no effect on the activity or expression of MRP1. Moreover, treatment with OA had no effect on the expression of the anti-apoptotic protein Bcl-2, but increased the expression of the pro-apoptotic protein Bax, altering the Bcl-2/Bax balance towards a pro-apoptotic profile. OA also decreased the expression of the anti-apoptotic protein survivin. Furthermore, OA decreased the expression of the angiogenic vascular endothelial growth factor (VEGF) and decreased the development of melanoma-induced lung metastasis. CONCLUSION: Our data provide a significant insight into the antitumoral and antimetastatic activity of OA in NSCLC and suggest that including OA in the NSCLC regimens may help to decrease the number of relapses and reduce the development of metastases.

Lipid metabolism modulation by the P2X7 receptor in the immune system and during the course of infection: new insights into the old view.

For decades, scientists have described numerous protein pathways and functions. Much of a protein's function depends on its interactions with different partners, and those partners can change depending on the cell type or system. The P2X7 receptor (P2X7R) is one such multifunctional protein that is related to multiple partners and signaling pathways. The relationship between P2X7R and different enzymes involved in lipid metabolism represents a relatively new field in P2X7R research. This field of research began in epithelial cells and currently includes immune and nervous cells. The P2X7R-lipid metabolism pathway is related to many biological functions of P2X7R, such as cell death and pathogen clearance, and this signaling pathway may be involved in many functions that are dependent on bioactive lipids. In the present review, we will attempt to summarize data related to the P2X7R-lipid metabolism pathway, focusing on signaling pathways and their biological relevance to the immune system and infection.

Immunohistochemical detection of Ki-67 is not associated with tumor-infiltrating macrophages and cyclooxygenase-2 in oral squamous cell carcinoma.

BACKGROUND: An inflammatory component consisting of cells and chemical mediators may influence the proliferation and dissemination of the oral squamous cell carcinoma (OSCC). In the present study, we evaluated the possible relationship between Ki-67, tumor-associated macrophages (TAMs), and COX-2 in OSCCs. In addition, the immunodetection of these proteins was associated with different histological grades of malignancy, including invasive and in situ tumors. METHODS: Twenty-seven OSCC cases were examined by light microscopy using criteria adopted WHO, and immunohistochemistry for Ki-67, CD68, and COX-2 using EnVision System in invasive and in situ lesions. Immunohistochemical detection of these proteins was assessed and scored for COX-2, and results were compared with their histological grades of malignancy. RESULTS: A correlation between Ki-67, COX-2, and CD68 was not found. Histological grade of malignancy (HDM) was associated with the Ki-67 immunostaining (P = 0.00), but this was not observed regarding both CD68 (P = 0.51) and COX-2 (P = 0.89). Furthermore, there was a COX-2 overexpression in 62.96% of the sample, and a high density of TAMs in both OSCCs and in situ carcinomas. CONCLUSIONS: Imunolabeling for Ki-67 was directly correlated with less-differentiated tumors, suggesting that this marker may contribute to understand the biological behavior of OSCC, and help to distinguish risk groups of OSCC. Furthermore, the lack of correlation between Ki-67, COX-2, and CD68 indicates that the latter two markers may play a pivotal role in oral carcinogenesis. However, further studies are needed to clarify their contribution for cell proliferation and tumor differentiation.