EGFR signaling-dependent inhibition of glioblastoma growth by ginsenoside Rh2

Abstract

Glioblastoma is the most common and most aggressive malignant primary brain tumor in humans, accounting for 52 % of all functional tissue brain tumor cases and 20 % of all intracranial tumors. The typical treatment involves a combination of chemotherapy, radiation, and surgery, whereas it still achieves fairly poor patient survival. Ginsenoside Rh2 has been reported to have a therapeutic effect on some tumors, but its effect on glioblastoma has not been extensively evaluated. Here, we show that ginsenoside Rh2 can substantially inhibit the growth of glioblastoma in vitro and in vivo in a mouse model. Moreover, the inhibition of the tumor growth appears to result from combined effects on decreased tumor cell proliferation and increased tumor cell apoptosis. Further analyses suggest that ginsenoside Rh2 may have its antiglioblastoma effect through inhibition of the epidermal growth factor receptor (EGFR) signaling pathway in tumor cells. In a lose-of-function experiment, recombinant EGFR was given together with ginsenoside Rh2 to the tumor cells in vitro and in vivo, which completely blocked the antitumor effects of ginsenoside Rh2. Thus, our data not only reveal an anti-glioblastoma effect of ginsenoside Rh2 but also demonstrate that this effect may function via inhibition of EGFR signaling in glioblastoma cells.

Ginsenoside Rh2 inhibits proliferation and induces apoptosis in human leukemia cells via TNF-α signaling pathway

“…In previous studies, it was found that ginsenoside Rh2 down-regulated EGFR and recombinant EGFR reduced anticancer activity of ginsenoside Rh2 in glioblastoma [29]. Ginsenoside Rh2 inhibited the growth of glioblastoma by binding EGFR competitively against EGF, and by inactivating EGFR/PI3k/Akt/mTOR signaling.…”

Ginsenoside Rh2 Mitigates Pediatric Leukemia Through Suppression of Bcl-2 in Leukemia Cells

“…Ginsenoside Rh2 (GRh2) is a well-characterized component in red ginseng, and has definite therapeutic effects on inflammation [11], abnormal vascularization [12], and some cancers [13][14][15][16], although the underlying mechanisms are still ill-defined. Nevertheless, whether GRh2 may be an effective treatment for pediatric leukemia has not been investigated.…”

Nuclear SMAD2 Restrains Proliferation of Glioblastoma

“…Since growth of GBM accounts for its major malignancy and detrimental effects on patients [1,2,3,4,5], here we aimed to elucidate the precise downstream signaling of an activated TGFβ receptor signaling on the growth of GBM cells [6,7,8,9,10,11,12,22,23,24,25,26,27,28,29,30,31]. …”

“…Glioblastoma multiforme (GBM), which is named as glioblastoma by WHO, is the most common and most malignant primary brain cancer in humans [1,2,3,4,5]. GBM is originated from glial cells and the patients suffer from an extremely low five-year survival ratio, which reasons from the relatively high invasiveness of GBM and the location of the tumor in the relatively closed central nervous system [1,2,3,4,5].…”

“…GBM is originated from glial cells and the patients suffer from an extremely low five-year survival ratio, which reasons from the relatively high invasiveness of GBM and the location of the tumor in the relatively closed central nervous system [1,2,3,4,5]. Hence, understanding of the molecular control of the growth of GBM represents one of the most important questions in the research in GBM, in which it may provide innovative therapy for the disease.…”