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Article

Ginsenoside 20(S)‑Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells

  • Authors:
    • Jie Li
    • Ting Liu
    • Le Zhao
    • Wei Chen
    • Huilian Hou
    • Zhongxue Ye
    • Xu Li
  • View Affiliations / Copyright

    Affiliations: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Center for Laboratory Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Pathology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
  • Pages: 775-781
    |
    Published online on: November 18, 2014
       https://doi.org/10.3892/ijo.2014.2767
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Abstract

Cancer cells prefer to metabolize glucose through aerobic glycolysis, known as the Warburg effect. It plays a crucial role in proliferation and progression of cancer cells. However, the complete mechanism remains elusive. In recent studies, the signal transducer and activator of transcription 3 (STAT3) signaling has been discovered to have roles in cancer‑associated changes in metabolism. In this study, we find that the ginsenoside 20(S)‑Rg3, a pharmacologically active component of the traditional Chinese herb Panax ginseng, inhibits glycolysis in ovarian cancer cells by regulating hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2). We also show that 20(S)‑Rg3 regulates HK2 through downregulation of p‑STAT3 (Tyr705). Furthermore, overexpression of STAT3 in ovarian cancer cells weakened the suppression of Warburg effect induced by 20(S)‑Rg3. Importantly, 20(S)‑Rg3 treatment represses HK2 expression in nude mouse xenograft models of ovarian cancer. Taken together, our results show that 20(S)‑Rg3 inhibits the Warburg effect by targeting STAT3/HK2 pathway in ovarian cancer cells, highlighting the potentiality of 20(S)‑Rg3 to be used as a therapeutic agent for ovarian cancer.
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1 

Cho KR and Shih IeM: Ovarian cancer. Annu Rev Pathol. 4:287–313. 2009. View Article : Google Scholar :

2 

Swisher EM, Taniguchi T and Karlan BY: Molecular scores to predict ovarian cancer outcomes: a worthy goal, but not ready for prime time. J Natl Cancer Inst. 104:642–645. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Gillis CN: Panax ginseng pharmacology: a nitric oxide link? Biochem Pharmacol. 54:1–8. 1997. View Article : Google Scholar : PubMed/NCBI

5 

Liao B, Newmark H and Zhou R: Neuroprotective effects of ginseng total saponin and ginsenosides Rb1 and Rg1 on spinal cord neurons in vitro. Exp Neurol. 173:224–234. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Nag SA, Qin JJ, Wang W, Wang MH, Wang H and Zhang R: Ginsenosides as anticancer agents: in vitro and in vivo activities, structure-activity relationships, and molecular mechanisms of action. Front Pharmacol. 3:252012. View Article : Google Scholar : PubMed/NCBI

7 

Lü JM, Yao Q and Chen C: Ginseng compounds: an update on their molecular mechanisms and medical applications. Curr Vasc Pharmacol. 7:293–302. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Lee SY, Kim GT, Roh SH, et al: Proteomic analysis of the anti-cancer effect of 20S-ginsenoside Rg3 in human colon cancer cell lines. Biosci Biotechnol Biochem. 73:811–816. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Mochizuki M, Yoo YC, Matsuzawa K, et al: Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside-Rb2, 20(R)- and 20(S)-ginsenoside-Rg3, of red ginseng. Biol Pharm Bull. 18:1197–1202. 1995. View Article : Google Scholar : PubMed/NCBI

10 

Bae EA, Kim EJ, Park JS, Kim HS, Ryu JH and Kim DH: Ginsenosides Rg3 and Rh2 inhibit the activation of AP-1 and protein kinase A pathway in lipopolysaccharide/interferon-gamma-stimulated BV-2 microglial cells. Planta Med. 72:627–633. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Keum YS, Han SS, Chun KS, et al: Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression, NF-kappaB activation and tumor promotion. Mutat Res. 523–524:75–85. 2003. View Article : Google Scholar

12 

Cui W, Cheng L, Hu C, Li H, Zhang Y and Chang J: Electrospun poly(L-lactide) fiber with ginsenoside rg3 for inhibiting scar hyperplasia of skin. PLoS One. 8:e687712013. View Article : Google Scholar : PubMed/NCBI

13 

Yue PY, Wong DY, Wu PK, et al: The angiosuppressive effects of 20(R)-ginsenoside Rg3. Biochem Pharmacol. 72:437–445. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956. View Article : Google Scholar : PubMed/NCBI

15 

Kim JW and Dang CV: Cancer’s molecular sweet tooth and the Warburg effect. Cancer Res. 66:8927–8930. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Vander Heiden MG, Cantley LC and Thompson CB: Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 324:1029–1033. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Diaz N, Minton S, Cox C, et al: Activation of stat3 in primary tumors from high-risk breast cancer patients is associated with elevated levels of activated SRC and survivin expression. Clin Cancer Res. 12:20–28. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Germain D and Frank DA: Targeting the cytoplasmic and nuclear functions of signal transducers and activators of transcription 3 for cancer therapy. Clin Cancer Res. 13:5665–5669. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Wang SW and Sun YM: The IL-6/JA K/STAT3 pathway: Potential therapeutic strategies in treating colorectal cancer (Review). Int J Oncol. 44:1032–1040. 2014.PubMed/NCBI

20 

Zhu Q, Hu J, Meng H, Shen Y, Zhou J and Zhu Z: S-phase cell cycle arrest, apoptosis, and molecular mechanisms of aplasia ras homolog member I-induced human ovarian cancer SKOV3 cell lines. Int J Gynecol Cancer. 24:629–634. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Jiang S, Zhang LF, Zhang HW, et al: A novel miR-155/miR-143 cascade controls glycolysis by regulating hexokinase 2 in breast cancer cells. EMBO J. 31:1985–1998. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Demaria M, Giorgi C, Lebiedzinska M, et al: A STAT3-mediated metabolic switch is involved in tumour transformation and STAT3 addiction. Aging (Albany NY). 2:823–842. 2010.

23 

Sawayama H, Ishimoto T, Sugihara H, et al: Clinical impact of the Warburg effect in gastrointestinal cancer (Review). Int J Oncol. 45:1345–1354. 2014.PubMed/NCBI

24 

Kiuchi N, Nakajima K, Ichiba M, et al: STAT3 is required for the gp130-mediated full activation of the c-myc gene. J Exp Med. 189:63–73. 1999. View Article : Google Scholar : PubMed/NCBI

25 

Ando M, Uehara I, Kogure K, et al: Interleukin 6 enhances glycolysis through expression of the glycolytic enzymes hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3. J Nippon Med Sch. 77:97–105. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Kim SM, Lee SY, Cho JS, et al: Combination of ginsenoside Rg3 with docetaxel enhances the susceptibility of prostate cancer cells via inhibition of NF-kappaB. Eur J Pharmacol. 631:1–9. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Lee JY, Jung KH, Morgan MJ, et al: Sensitization of TRAIL-induced cell death by 20(S)-ginsenoside Rg3 via CHOP-mediated DR5 upregulation in human hepatocellular carcinoma cells. Mol Cancer Ther. 12:274–285. 2013. View Article : Google Scholar

28 

Liu CY, Tseng LM, Su JC, et al: Novel sorafenib analogues induce apoptosis through SHP-1 dependent STAT3 inactivation in human breast cancer cells. Breast Cancer Res. 15:R632013. View Article : Google Scholar : PubMed/NCBI

29 

Mathupala SP, Ko YH and Pedersen PL: Hexokinase-2 bound to mitochondria: cancer’s stygian link to the ‘Warburg Effect’ and a pivotal target for effective therapy. Semin Cancer Biol. 19:17–24. 2009. View Article : Google Scholar :

30 

Vander Heiden MG, Lunt SY, Dayton TL, et al: Metabolic pathway alterations that support cell proliferation. Cold Spring Harb Symp Quant Biol. 76:325–334. 2011. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Li J, Liu T, Zhao L, Chen W, Hou H, Ye Z and Li X: Ginsenoside 20(S)‑Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells. Int J Oncol 46: 775-781, 2015.
APA
Li, J., Liu, T., Zhao, L., Chen, W., Hou, H., Ye, Z., & Li, X. (2015). Ginsenoside 20(S)‑Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells. International Journal of Oncology, 46, 775-781. https://doi.org/10.3892/ijo.2014.2767
MLA
Li, J., Liu, T., Zhao, L., Chen, W., Hou, H., Ye, Z., Li, X."Ginsenoside 20(S)‑Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells". International Journal of Oncology 46.2 (2015): 775-781.
Chicago
Li, J., Liu, T., Zhao, L., Chen, W., Hou, H., Ye, Z., Li, X."Ginsenoside 20(S)‑Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells". International Journal of Oncology 46, no. 2 (2015): 775-781. https://doi.org/10.3892/ijo.2014.2767
Copy and paste a formatted citation
x
Spandidos Publications style
Li J, Liu T, Zhao L, Chen W, Hou H, Ye Z and Li X: Ginsenoside 20(S)‑Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells. Int J Oncol 46: 775-781, 2015.
APA
Li, J., Liu, T., Zhao, L., Chen, W., Hou, H., Ye, Z., & Li, X. (2015). Ginsenoside 20(S)‑Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells. International Journal of Oncology, 46, 775-781. https://doi.org/10.3892/ijo.2014.2767
MLA
Li, J., Liu, T., Zhao, L., Chen, W., Hou, H., Ye, Z., Li, X."Ginsenoside 20(S)‑Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells". International Journal of Oncology 46.2 (2015): 775-781.
Chicago
Li, J., Liu, T., Zhao, L., Chen, W., Hou, H., Ye, Z., Li, X."Ginsenoside 20(S)‑Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells". International Journal of Oncology 46, no. 2 (2015): 775-781. https://doi.org/10.3892/ijo.2014.2767
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