Swelling-induced chloride current in glioblastoma proliferation, migration, and invasion.

Glioblastoma (GBM) remains as the most common and aggressive brain tumor. The survival of GBM has been linked to the aberrant activation of swelling-induced chloride current ICl,swell . In this study, we investigated the effects of ICl,swell on cell viability, proliferation, and migration in the human GBM cell lines, U251 and U87, using a combination of patch clamp electrophysiology, MTT, colony formation, wound healing assays and Western immunoblotting. First, we showed that the specific inhibitor of ICl,swell , DCPIB, potently reduced the ICl,swell in U87 cells. Next, in both U87 and U251 cells, we found that DCPIB reduced GBM viability, proliferation, colony formation, migration, and invasion. In addition, our Western immunoblot assay showed that DCPIB-treated U251 cells had a reduction in JAK2, STAT3, and Akt phosphorylation, thus, suggesting that DCPIB potentially suppresses GBM functions through inhibition of the JAK2/STAT3 and PI3K/Akt signaling pathways. Therefore, the ICl,swell may be a potential drug target for GBM.

Wong R ，Chen W ，Zhong X ，Rutka JT ，Feng ZP ，Sun HS ... -  《-》

Inhibition of TRPM7 by carvacrol suppresses glioblastoma cell proliferation, migration and invasion.

Chen WL ，Barszczyk A ，Turlova E ，Deurloo M ，Liu B ，Yang BB ，Rutka JT ，Feng ZP ，Sun HS ... -  《Oncotarget》

Activation of TRPM7 by naltriben enhances migration and invasion of glioblastoma cells.

Wong R ，Turlova E ，Feng ZP ，Rutka JT ，Sun HS ... -  《Oncotarget》

Xyloketal B suppresses glioblastoma cell proliferation and migration in vitro through inhibiting TRPM7-regulated PI3K/Akt and MEK/ERK signaling pathways.

Chen WL ，Turlova E ，Sun CL ，Kim JS ，Huang S ，Zhong X ，Guan YY ，Wang GL ，Rutka JT ，Feng ZP ，Sun HS ... -  《Marine Drugs》

Demethoxycurcumin Suppresses Proliferation, Migration, and Invasion of Human Brain Glioblastoma Multiforme GBM 8401 Cells via PI3K/Akt Pathway.

Demethoxycurcumin (DMC), one of the derivatives of curcumin, has been shown to induce apoptotic cell death in many human cancer cell lines. However, there is no available information on whether DMC inhibits metastatic activity in human glioblastoma cancer cells in vitro. DMC at 1.0-3.0 μM significantly decreased the proliferation of GBM 8401 cells; thus, we used 2.0 μM for further investigation regarding anti-metastatic activity in human glioblastoma GBM 8401 cells. The internalized amount of DMC has reached the highest level in GBM 8401 cells after 3 h treatment. Wound healing assay was used to determine cell mobility and results indicated that DMC suppressed cell movement of GBM 8401 cells. The transwell chamber assays were used for measuring cell migration and invasion and results indicated that DMC suppressed cell migration and invasion in GBM 8401 cells. Gelatin zymography assay was used to examine gelatinolytic activity (MMP-2) in conditioned media of GBM 8401 cells treated by DMC and results demonstrated that DMC significantly reduced MMP-2 activity. Western blotting showed that DMC reduced the levels of p-EGFR(Tyr1068), GRB2, Sos1, p-Raf, MEK, p-ERK1/2, PI3K, p-Akt/PKBα(Thr308), p-PDK1, NF-κB, TIMP-1, MMP-9, MMP-2, GSK3α/β, β-catenin, N-cadherin, and vimentin, but it elevated Ras and E-cadherin at 24 h treatment. DMC inhibited cancer cell migration and invasion through inhibition of PI3K/Akt and NF-κB signaling pathways in GBM 8401 cells. We suggest that DMC may be used as a novel anti-metastasis agent for the treatment of human glioblastoma cancer in the future.

Su RY ，Hsueh SC ，Chen CY ，Hsu MJ ，Lu HF ，Peng SF ，Chen PY ，Lien JC ，Chen YL ，Chueh FS ，Chung JG ，Yeh MY ，Huang YP ... -  《-》