Lysophosphatidic Acid Upregulates Recepteur D'origine Nantais Expression and Cell Invasion via Egr-1, AP-1, and NF-κB Signaling in Bladder Carcinoma Cells.

Muscle invasive bladder carcinoma is a highly malignant cancer with a high mortality rate, due to its tendency to metastasize. The tyrosine kinase recepteur d'origine nantais (RON) promotes bladder carcinoma metastasis. Lysophosphatidic acid (LPA) is a phospholipid derivative, which acts as a signaling molecule to activate three high affinity G-protein coupled receptors, LPA1, LPA2, and LPA3. This in turn leads to cell proliferation and contributes to oncogenesis. However, little is known about the effects of LPA on invasive bladder cancer (IBC). In this study, we discovered that LPA upregulated RON expression, which in turn promoted cell invasion in bladder cancer T24 cells. As expected, we found that the LPA receptor was essential for the LPA induced increase in RON expression. More interestingly, we discovered that LPA induced RON expression via the MAPK (ERK1/2, JNK1/2), Egr-1, AP-1, and NF-κB signaling axes. These results provide experimental evidence and novel insights regarding bladder malignancy metastasis, which could be helpful for developing new therapeutic strategies for IBC treatment.

Prostate Cancer Cell-Specific Cytotoxicity of Sub-Micron Potassium Niobate Powder.

Oxide nanoparticles have numerous potential applications in medicine such as carriers for therapeutic drugs, contrast agents for bio-imaging and targeting agents for tumors. Oxide nanoparticles may also have an inherent cytotoxicity towards cancer cells, as recently found for cerium oxide. KNbO3 nanoparticles have a combination of low toxicity and nonlinear optical properties which make them attractive for use as a bio-imaging material. However, little is known yet about the cytotoxicity of KNbO3 particles towards cancerous cells. In the present work, the cytotoxicity of KNbO3 particles to normal and prostate cancer cell lines is studied. The mixed oxide method is used to prepare KNbO3 powder. Using dynamic light scattering the mean particle diameter of the KNbO3 powder is found to be ∼500 nm. X-ray diffraction, Fourier transform infra-red spectroscopy and Raman scattering spectroscopy are used to examine the structure of the KNbO3 powder. Powder morphology is examined using scanning electron microscopy. MTT assays of EA.hy926, PC-3 and DU-145 cell lines are carried out to study cell-specific cytotoxicity. KNbO3 sub-micron particles are found to have low toxicity to PC-3 cells, moderate toxicity to EA.hy926 cells and high toxicity to DU-145 cells. A new avenue towards the treatment of prostate cancer may be opened by the cell-specific cytotoxicity of KNbO3.

Apigenin Suppresses the IL-1ß-Induced Expression of the Urokinase-Type Plasminogen Activator Receptor by Inhibiting MAPK-Mediated AP-1 and NF-κB Signaling in Human Bladder Cancer T24 Cells.

The urokinase-type plasminogen activator receptor (uPAR), a glycoprotein localized on the cell surface with a glycosylphosphatidylinositol anchor, plays a crucial role in cell invasion, and the metastasis of several cancers, including bladder cancer, and its expression are significantly negatively correlated with patient survival rates. Apigenin, a naturally produced phytochemical compound found in fruits, vegetables, and plant leaves, has been shown to mediate a variety of cancer-metastasis-related molecules in various cancers. The effect of apigenin on uPAR expression is still unknown. In this study, we examined the effects of apigenin on IL-1ß-induced uPAR expression and investigated its potential mechanisms. We discovered in this study that IL-1ß could remarkably induce uPAR expression in bladder cancer T24 cells and that apigenin-inhibited IL-1ß could induce uPAR expression concentration-dependently. Interestingly, NF-κB and AP-1 transcription factors were critically required for IL-1ß-induced high uPAR expression. Apigenin suppressed the transcriptional activity of both AP-1 and NF-κB by inhibiting ERK1/2 and JNK signaling pathways. These results suggest that apigenin can exert anti-invasion effects by inhibiting uPAR expression via mediating (ERK1/2, JNK)/AP-1 and (ERK1/2, JNK)/NF-κB signaling pathways in human T24 cells. Our present study generated novel and valuable biological insight into anti-invasion through treatment with a small native compound.