Anti-Cancer Effect of Ginsenoside F₂against Glioblastoma Multiforme in Xenograft Model in SD Rats

Abstract

The glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Despite combination treatments of radiation and chemotherapy, the survival periods are very short. Therefore, this study was conducted to assess the potential of ginsenoside F2 (F2) to treat GBM. In in vitro experiments with glioblastoma cells U373MG, F2 showed the cytotoxic effect with IC50 of 50 μg/mL through apoptosis, confirmed by DNA condensation and fragmentation. The cell population of cell cycle sub-G1 as indicative of apoptosis was also increased. In xenograft model in SD rats, F2 at dosage of 35 mg/kg weight was intravenously injected every two days. This reduced the tumor growth in magnetic resonance imaging images. The immunohistochemistry revealed that the anticancer activity might be mediated through inhibition of proliferation judged by Ki67 and apoptosis induced by activation of caspase-3 and -8. And the lowered expression of CD31 showed the reduction in blood vessel densities. The expression of matrix metalloproteinase-9 for invasion of cancer was also inhibited. The cell populations with cancer stem cell markers of CD133 and nestin were reduced. The results of this study suggested that F2 could be a new potential chemotherapeutic drug for GBM treatment by inhibiting the growth and invasion of cancer.

Inhibition of autophagosome-lysosome fusion by ginsenoside Ro via the ESR2-NCF1-ROS pathway sensitizes esophageal cancer cells to 5-fluorouracil-induced cell death via the CHEK1-mediated DNA damage checkpoint

“…Several ginsenosides such as ginsenoside Rg3, Rh2, Re, and F2, have been tested in vitro and in vivo as novel anticancer agents to induce apoptosis and inhibit cell proliferation and metastasis. 22,23 Many molecular mechanisms have been proposed for such anticancer activity, Downloaded by [University of Cambridge] at 17:58 16 June 2016 6 including autophagy regulation. [24][25][26][27] Moreover, autophagy contributes to the neuronal protective effects of ginsenoside Rb1 and compound K. 28,29 However, there is currently no evidence showing a direct connection between autophagy and ginsenoside-induced cell death.…”

Ginsenoside F2 Reduces Hair Loss by Controlling Apoptosis through the Sterol Regulatory Element-Binding Protein Cleavage Activating Protein and Transforming Growth Factor-β Pathways in a Dihydrotestosterone-Induced Mouse Model

“…12,13) Ginsenoside Rb1, precursor of ginsenoside F2, has been reported to prevent apoptosis induced by external stimuli in human keratinocyte cells (HaCaTs) as well as to inhibit activation by DHT. 14,15) However, the effects of ginsenoside F2 on hair loss have not been reported.…”

iTRAQ‐Based Proteomic Analysis of Ginsenoside F2 on Human Gastric Carcinoma Cells SGC7901

“…Currently, chemotherapy has proved to decrease the rate of recurrence and improve overall survival; however, the drug resistance and serious toxic side effects largely reduce therapeutic efficacy and quality of life in patients [2, 3]. In recent years, compounds of natural products have caught wide attention due to their promising anticancer effects and minimal side effects [4–7]. Therefore, it is very necessary to develop new optimal anticancer agent from natural resource [3].…”

“…Exploration of ginsenoside as a new anticarcinogenic agent is of much interest [4–7]. Structural-function studies showed that the increased antitumor effect is implicated with the decrease of its sugar number [5].…”