Ginsenoside Rh2 inhibits glioma cell proliferation by targeting microRNA-128

Abstract

Aim: To examine the influence of ginsenoside Rh2 (Rh2), a triterpene saponin extracted from the traditional medicinal plant ginseng, on the expression of miRNAs in human glioma cells. Methods: The expression profile of miRNA (miR) was analyzed in human U251, T98MG and A172 glioma cells using a miRNA array and quantitative real-time PCR. Cell viability was assessed using a colorimetric assay (cell counting kit-8). Transfection of miR-128 was performed using Lipofectamine 2000. Caspase 3 activity was determined using a caspase colorimetric assay kit. Apoptosis was assessed using annexin V and propidium iodide staining. Protein expression was determined with Western blot analysis. miRNA-128 targeting activity was measured using a luciferase reporter assay. Results: In U251 cells treated with Rh2 (12 μg/mL), 14 of 452 human miRNAs were up-regulated and 12 were down-regulated as detected with the miRNA array assay. The up-regulation of miR-128 by Rh2 was further verified in human U251, T98MG and A172 cells using quantitative real-time PCR. In U251 cells, transfection of a miR-128 inhibitor (50 nmol/L) prevented the overexpression of miR-128 by Rh2, and significantly blunted Rh2-induced cytotoxicity, apoptosis, caspase 3 activation, transcriptional activation of E2F3a, a miR-128 target gene, as well as E2F3a protein expression. Conclusion: The anti-proliferative effect of Rh2 in human glioma cells was mediated in part through up-regulation of miRNA-128 expression.

Ginsenoside Rh2 mediates changes in the microRNA expression profile of human non-small cell lung cancer A549 cells

“…In order to identify additional molecular pathways participating in the anticancer effect of Rh2, we performed miRNA expression profiling analysis with the aim to detect specific regulators of the Rh2-mediated anticancer properties in NSCLCs. On the basis of a recent report that Rh2 inhibits glioma cell proliferation by targeting miR-128, it is considered a novel mechanism for the anticancer effect of Rh2 (13). In the present study, we discovered that the expression of specific miRNAs in Rh2-treated A549 cells was significantly altered when compared to that in the untreated A549 (control) cells (Fig.…”

“…Several health benefits of Rh2 have been reported due to its anti-inflammatory, antiGinsenoside Rh2 mediates changes in the microRNA expression profile of human non-small cell lung cancer A549 cells osteoclastogenic, anti-hyperglycemic and anticancer effects (10)(11)(12)(13)(14). The anticancer effect of Rh2 has been particularly observed in NSCLCs.…”

Pharmacokinetic interactions between 20(S)-ginsenoside Rh2 and the HIV protease inhibitor ritonavir in vitro and in vivo

“…Despite the clinic significance of PIs, accumulating clinical evidence indicates that the incorporation of HIV PIs into HAART is associated with various adverse effects, such as metabolic syndrome characterized by dyslipidemia, insulin resistance, and lipodystrophy [2,3] . 20(S)-Ginsenoside Rh2 (Rh2), a component isolated from red ginseng [4] , is one of the most studied ginsenosides due to its various pharmacological activities, such as anti-cancer effects, anti-hyperglycemic effects, and anti-obesity effects [5][6][7][8] . Rh2 has been approved as a complementary food by the China State Food and Drug Administration since 2006, and it can be speculated that Rh2 is popular among HIV-infected patients, especially in the individuals with AIDS and cancer.…”

20(<i>S</i>)-Ginsenoside Rh2 Induces Apoptosis in Human Leukaemia Reh Cells through Mitochondrial Signaling Pathways

“…[11][12][13] Recently, researchers have found that 20(S)-GRh2 exhibits anticancer effects and could inhibit growth of several cancer cell lines and induce apoptosis in mammalian tumor cells. [14][15][16] However, the details of the signal transduction cascade involved in 20(S)-GRh2-induced death in Reh cells remaine unclear.…”