Prostate cancer develops in the prostate, which is a gland in the male reproductive system. Prostate cancers generally grow slowly. However, aggressive prostate cancers do occur, which are capable of metastasizing from the prostate to other parts of the body, particularly the bones and lymph nodes. Transforming growth factor β (TGFβ) signaling pathway has been shown to play a critical role in the tumorigenesis of prostate cancer. TGFβ signaling pathways are involved in many biological events. SMAD2 and SMAD3 are key plays that typically mediate TGFβ receptor signaling. They are phosphorylated by the activated TGFβ receptor I in the cytosol (pSMAD2 and pSMAD3) and then translocate into the nucleus to exert many biological functions through directly binding to the DNA. Specifically, pSMAD2 and pSMAD3 have been shown to inhibit cell growth through regulation of cell-cycle controllers.Moreover, they may regulate matrix metalloproteinases (MMPs) to control cell metastasis.
Ginsenoside Rh2 (GRh2) is one of the characteristic components in red ginseng with potential bioactivity. GRh2 has been shown to have potentially therapeutic effects on various cancers and on enteritis. Nevertheless, the exact molecular basis of the anti-tumor effect of GRh2 remains unclear. Here, we show that GRh2 can substantially inhibit the growth of prostatic cancer in vivo and in vitro, resulting from a combined inhibitory effect on tumor cell proliferation and tumor cell invasiveness. Further, GRh2 seemed to activate TGFβ receptor signaling in prostatic cancer cells, which subsequently inhibits cell proliferation and invasion through regulating cell cycle controllers and MMPs, respectively.
Materials and methods
Culture and label human prostatic cancer cell line with a luciferase reporter Human prostatic cancer cell line PC3 has been described before and was maintained in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10 % fetal bovine serum. To trace the PC3 cells in vivo, we infected the cells with a recombinant lentivirus expressing luciferease and GFP under the control of CMV promoter at MOI 100 and resulted in nearly 100 % infection efficiency based on green fluorescence. The reporter-carrying PC3 cells were termed PC3-luc. GRh2 (0.1 mg/ml) was given to the cultured cells for intervention.
Mouse manipulations
Twelve-week-old male nude mice were used for experiments. GRh2 (1 mg/kg body weight) was injected from the tail vein of the mice twice per week for 4 weeks until the end of the experiment. Controlmice received saline injection of same volume.
Induction of prostatic cancer
PC3-luc cells (105) were stereotactically implanted into the prostate of 12-week-old male nude mice as has been previously described. One month after, the animals were examined of tumor growth by luciferin assay.
Results
GRh2 efficiently inhibited the growth of prostatic cancer in vivo Human prostatic cancer cell line PC3 has been described before and was used in the current study. To trace the PC3 cells in vivo, we infected the cells with a recombinant lentivirus expressing luciferease and GFP under the control of CMV promoter at MOI 100 and resulted in nearly 100 % infection efficiency based on green fluorescence. The reporter-carrying PC3-luc cells were stereotactically injected into the prostate of 12-week-old male nude mice. GRh2 was then intravenously administrated at a concentration of 1mg/kg body weight to the mice, twice per week for 4 weeks. The control mice received injection of saline of same volume. After 4 weeks, the animals were examined of tumor growth by luciferin assay. We found that the bioluminescence levels in the GRh2-treated mice were lower than those in control mice by 83.5±10.5 %, suggesting that GRh2 efficiently inhibited the growth of prostatic cancer in vivo.
Reference:
Qingchuan Zhang & Bin Hong & Songhua Wu & Tianli Niu. Tumor Biol. (2015) 36:2377–2381
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| CAS Number | Product Name | Molecular Formula | Molecular Weight | Description |
| 14197-60-5 | Ginsenoside Rg3 | C42H72O13 | 785.01 | Ginsenoside Rg3 is a natural product isolated from Panax ginseng. Similar to other ginsenosides it exhibits cardio protective effects. Ginsenoside Rg3 enhances cardiac, hERG (IKr) and KCNQ (Iks), channel currents by interaction with the channel pore entryway. It also inhibits the palmitate-induced apoptosis of MIN6N8 mouse insulinoma beta-cells through modulating p44/42 MAPK activation. Ginsenoside Rg3 increases the level of the transcription factor Nrf2 and induces the mRNA levels of multidrug resistance-associated protein (Mrp) and Mrp3.1 Rg3 modulate neuroinflammation by attenuating the activation of microglia in response to systemic LPS treatment. It activates AMPK in HepG2 cells and reduces the lipid accumulation thereby decreasing the risk of cardiovascular disease due to dyslipidemia. |
| 78214-33-2 | Ginsenoside Rh2 | C36H62O8 | 622 | Ginsenoside Rh2 is extrected from the roots of Panax ginseng C. A. Mey. It has anti-cancer proliferation, differentiation and chemopreventive effects in certain cancer cell types. It suppresses the growth of A375-S2 cells in vitro by inducing apoptosis. It had the most potent inhibitory activity on β-hexosaminidase release from RBL-2H3 cells and in the passive cutaneous anaphylaxis reaction. It can exhibit antiallergic activity originating from cell membrane-stabilizing activity and antiinflammatory activity by the inhibition of NO and PGE2 production. |
| 51542-56-4 | Ginsenoside | C48H82O18 | 946 | Ginsenoside Re is a phytosterol found in the ginseng root. It is believed to be the main contributor to ginseng′s protection against damage from cardiac ischemia by inhibiting calcium accumulation in the mitochondria. It inhibits calcium buildup through activation of endothelial nitric oxide synthase (eNOS) to release NO and activate delayed rectifier K+ currents. It improves the effectiveness of chemotherapeutic agents by decreasing the expression of Multidrug Resistance Protein 1 and inhibiting P-glycoprotein. |