Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation

Abstract

Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to have a radiosensitization effect on tumors. However, its effects on human glioma and the specific molecular mechanisms of these effects remain unknown. In this study, we demonstrated that Tet has a radiosensitization effect on human glioma cells. It has been hypothesized that Tet has a radiosensitization effect on glioma cells by affecting the glioma cell cycle and DNA repair mechanism and that ERK mediates these activities. Therefore, we conducted detailed analyses of the effects of Tet on the cell cycle by performing flow cytometric analysis and on DNA repair by detecting the expression of phosphorylated H2AX by immunofluorescence. We used western blot analysis to investigate the role of ERK in the effect of Tet on the cell cycle and DNA repair. The results revealed that Tet exerts its radiosensitization effect on glioma cells by inhibiting proliferation and decreasing the expression of phosphorylated ERK and its downstream proteins. In summary, our data indicate that ERK is involved in Tet-induced radiosensitization of glioma cells via inhibition of glioma cell proliferation or of the cell cycle at G0/G1 phase.

Involvement of P2X7 Receptor in Proliferation and Migration of Human Glioma Cells

“…In tumor cells, members of the MEK/ERK pathway encoding genes are often mutated and become overactivated, which causes this pathway to be important for the development of many human tumors such as breast cancer, thyroid carcinoma, and squamous cell carcinoma [ 46 , 47 ]. The MEK/ERK pathway also plays a critical role in the development of gliomas [ 24 , 48 , 49 ]. The MEK/ERK pathway is involved in purinergic receptor, such as P2X 7 R, mediated excitotoxic neuronal injury, and neuroprotection [ 50 ].…”

Natural products: a hope for glioblastoma patients

“…Interestingly, multiple compounds from natural sources namely resveratrol, icariin, quercetin, propolisis, Turmeric Force™ and Withaferin A work synergistically with TMZ [ 28 , 32 , 33 , 37 , 49 , 53 , 205 ]. Zataria multiflora hydroalcoholic extract and Tet also significantly increased the radiosensitivity of the A172 and the U87 and U251 GBM cell lines respectively [ 86 , 88 ]. Resveratrol, Withaferin A , quercetin, methanolic extract of Salvia menthaefolia roots, berberine, Ficus carica latex, propolisis, AMT, thymoquinone and cucurbitacins efficiently blocked cell proliferation and induced apoptosis, even in the TMZ resistant GBM cell lines [ 27 , 32 , 42 , 49 , 53 , 113 , 125 , 188 , 190 , 236 ].…”

“…Tetrandrine (Tet) is a bisbenzylisoquinoline alkaloid that is isolated from the roots of Stephania tetrandra S. Moore , with known apoptotic, anti-angiogenic and radiosensitizing properties in many cancers [ 87 , 88 ]. Recently, Tet was also shown to radiosensitize GBM cells U87 and U251 by significantly inhibiting their proliferation via inducing G 0 /G 1 cell cycle arrest, attenuating the radiation induced ERK signaling pathway and decreased expression of proliferation associated genes PCNA and cyclin D1 [ 88 ].…”

TBX2 overexpression promotes proliferation and invasion through epithelial‑mesenchymal transition and ERK signaling pathway

“…Level of p-ERK increased in SGC-7901 cells transfected with TBX2, while p-ERK level decreased in BGC-823 cells interferenced with TBX2 siRNA. The ERK cascade functions in cellular proliferation, differentiation, and survival, and its activation promotes tumor progression (47–50). We speculated that regulatory effect of TBX2 in GC may partly depend on ERK signaling pathway.…”