Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Down-regulation of Phosphoglucose Isomerase/Autocrine Motility Factor Enhances Gensenoside Rh2 Pharmacological Action on Leukemia KG1α Cells

  • You, Zhi-Mei (Laboratory of Stem Cells and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University) ;
  • Zhao, Liang (Laboratory of Stem Cells and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University) ;
  • Xia, Jing (Laboratory of Stem Cells and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University) ;
  • Wei, Qiang (Laboratory of Stem Cells and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University) ;
  • Liu, Yu-Min (College of Pharmacy, the First Affiliated Hospital, Chongqing Medical University) ;
  • Liu, Xiao-Yan (Department of Geriatrics, the First Affiliated Hospital, Chongqing Medical University) ;
  • Chen, Di-Long (Laboratory of Stem Cells and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University) ;
  • Li, Jing (Laboratory of Stem Cells and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University)
  • Published : 2014.02.01
Download PDF
⟨ Previous Next ⟩

Abstract

Aims and Background: Ginsenoside Rh2, which exerts the potent anticancer action both in vitro and in vivo, is one of the most well characterized ginsenosides extracted from ginseng. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between ginsenoside Rh2 and phosphoglucose isomerase/autocrine motility factor (PGI/AMF). Methods: $KG1{\alpha}$, a leukemia cell line highly expressing PGI/AMF was assessed by western blot analysis and reverse transcription- PCR (RT-PCR) assay after transfection of a small interfering (si)-RNA to silence PGI/AMF. The effect of PGI/AMF on proliferation was measured by typan blue assay and antibody array. A cell counting kit (CCK)-8 and flow cytometry (FCM) were adopted to investigate the effects of Rh2 on PGI/AMF. The relationships between PGI/AMF and Rh2 associated with Akt, mTOR, Raptor, Rag were detected by western blot analysis. Results: KG1${\alpha}$ cells expressed PGI/AMF and its down-regulation significantly inhibited proliferation. The antibody array indicated that the probable mechanism was reduced expression of PARP, State1, SAPK/JNK and Erk1/2, while those of PRAS40 and p38 were up-regulated. Silencing of PGI/AMF enhanced the sensibility of $KG1{\alpha}$ to Rh2 by suppressing the expression of mTOR, Raptor and Akt. Conclusion: These results suggested that ginsenoside Rh2 suppressed the proliferation of $KG1{\alpha}$, the same as down-regulation of PGI/AMF. Down-regulation of PGI/AMF enhanced the pharmacological effects of ginsenoside Rh2 on KG1${\alpha}$ by reducing Akt/mTOR signaling.

Keywords

References

  1. Cao MJ, Osatomi K, Matsuda R, et al (2000). Purification of a novel serine proteinase inhibitor from the skeletal muscle of white croaker (Argyrosomus argentatus). Biochem Biophys Res Commun, 272, 485-89. https://doi.org/10.1006/bbrc.2000.2803
  2. Cheng CC, Yang SM, Huang CY, et al (2005). Molecular mechanisms of ginsenoside Rh2-mediated G1 growth arrest and apoptosis in human lung adenocarcinoma A549 cells. Cancer Chemother Pharmacol, 55, 531-40. https://doi.org/10.1007/s00280-004-0919-6
  3. Christensen, LP (2009). Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutrition Res, 55, 1-99.
  4. Chung KS, Cho SH, Shin JS, et al (2013). Ginsenoside Rh2 induces cell cycle arrest and differentiation in human leukemia cells by upregulating TGF-beta expression. Carcinogenesis, 34, 331-40. https://doi.org/10.1093/carcin/bgs341
  5. Dennis PB, Jaeschke A, Saitoh M, et al (2001). Mammalian TOR: a homeostatic ATP sensor. Science, 294, 1102-5. https://doi.org/10.1126/science.1063518
  6. Fu M, Li L, Albrecht T, et al (2011). Autocrine motility factor/phosphoglucose isomerase regulates ER stress and cell death through control of ER calcium release. Cell Death Differ, 18, 1057-70. https://doi.org/10.1038/cdd.2010.181
  7. Funasaka T, Hogan V, Raz A (2009). Phosphoglucose isomerase/autocrine motility factor mediates epithelial and mesenchymal phenotype conversions in breast cancer. Cancer Res, 69, 5349-56. https://doi.org/10.1158/0008-5472.CAN-09-0488
  8. Funasaka T, Hu H, Hogan V, et al (2007). Down-regulation of phosphoglucose isomerase/autocrine motility factor expression sensitizes human fibrosarcoma cells to oxidative stress leading to cellular senescence. Journal Chem, 282, 36362-9.
  9. Funasaka T, Hu H, Yanagawa T, et al (2007). Down-regulation of phosphoglucose isomerase/autocrine motility factor results in mesenchymal-to-epithelial transition of human lung fibrosarcoma cells. Cancer Res, 67, 4236-43. https://doi.org/10.1158/0008-5472.CAN-06-3935
  10. Gingras AC, Raught B, Sonenberg N (2001). Regulation of translation initiation by FRAP/mTOR. Genes Dev, 15, 807-26. https://doi.org/10.1101/gad.887201
  11. Guarino M (2007). Epithelial-mesenchymal transition and tumour invasion. Int J Biochem Cell bio, 39, 2153-60. https://doi.org/10.1016/j.biocel.2007.07.011
  12. Gwinn DM, Shackelford DB, Egan DF, et al (2008). AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell, 30, 214-26. https://doi.org/10.1016/j.molcel.2008.03.003
  13. Haga A, Funasaka T, Niinaka Y, et al (2003). Autocrine motility factor signaling induces tumor apoptotic resistance by regulations Apaf-1 and Caspase-9 apoptosome expression. International journal of cancer. Int J Cancer, 107, 707-14. https://doi.org/10.1002/ijc.11449
  14. Helms S (2004). Cancer prevention and therapeutics: Panax ginseng. Alter Med Rev, 9, 259-74.
  15. Huang S, Houghton PJ (2003). Targeting mTOR signaling for cancer therapy. Cur Opin Pharmacol, 3, 371-7. https://doi.org/10.1016/S1471-4892(03)00071-7
  16. Kho DH, Nangia-Makker P, Balan V, et al (2013). Autocrine motility factor promotes HER2 cleavage and signaling in breast cancer cells. Cancer Res, 73, 1411-9. https://doi.org/10.1158/0008-5472.CAN-12-2149
  17. Kovacina KS, Park GY, Bae SS, et al (2003). Identification of a proline-rich Akt substrate as a 14-3-3 binding partner. J Biol Chem, 278, 10189-94. https://doi.org/10.1074/jbc.M210837200
  18. Lee JM, Dedhar S, Kalluri R, et al (2006). The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol, 172, 973-81. https://doi.org/10.1083/jcb.200601018
  19. Li B, Zhao J, Wang CZ, et al (2011). Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53. Cancer lett, 301, 185-92. https://doi.org/10.1016/j.canlet.2010.11.015
  20. Matsumoto I, Staub A, Benoist C, et al (1999). Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme. Science, 286, 1732-5. https://doi.org/10.1126/science.286.5445.1732
  21. Nicholson KM, Anderson NG (2002). The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal, 14, 381-95. https://doi.org/10.1016/S0898-6568(01)00271-6
  22. Niinaka Y, Harada K, Fujimuro M, et al (2010). Silencing of autocrine motility factor induces mesenchymal-to-epithelial transition and suppression of osteosarcoma pulmonary metastasis. Cancer Res, 70, 9483-93. https://doi.org/10.1158/0008-5472.CAN-09-3880
  23. Park EK, Lee EJ, Lee SH, et al (2010). Induction of apoptosis by the ginsenoside Rh2 by internalization of lipid rafts and caveolae and inactivation of Akt. Br J Pharmacol, 160, 1212-23. https://doi.org/10.1111/j.1476-5381.2010.00768.x
  24. Park HM, Kim SJ, Kim JS, et al (2012). Reactive oxygen species mediated ginsenoside Rg3- and Rh2-induced apoptosis in hepatoma cells through mitochondrial signaling pathways. Food Chem Toxicol, 50, 2736-41. https://doi.org/10.1016/j.fct.2012.05.027
  25. Sancak Y, Thoreen CC, Peterson TR, et al, (2007). PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell, 25, 903-15. https://doi.org/10.1016/j.molcel.2007.03.003
  26. Shih WL, Yu FL, Chang CD, et al (2012). Suppression of AMF/PGI-mediated tumorigenic activities by ursolic acid in cultured hepatoma cells and in a mouse model. Mol Carcinog, 52, 800-12
  27. Tang XP, Tang GD, Fang CY, et al (2013). Effects of ginsenoside Rh2 on growth and migration of pancreatic cancer cells. World J Gastroenterol, 19, 1582-92. https://doi.org/10.3748/wjg.v19.i10.1582
  28. Thiery JP, Sleeman JP (2006). Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol, 7, 131-42. https://doi.org/10.1038/nrm1835
  29. Tsutsumi S, Hogan V, Nabi IR, et al (2003). Overexpression of the autocrine motility factor/phosphoglucose isomerase induces transformation and survival of NIH-3T3 fibroblasts. Cancer Res, 63, 242-9.
  30. Tsutsumi S, Yanagawa T, Shimura T, et al (2003). Regulation of cell proliferation by autocrine motility factor/phosphoglucose isomerase signaling. J Biol Chem, 278, 32165-72. https://doi.org/10.1074/jbc.M304537200
  31. Vander Haar E, Lee SI, Bandhakavi S, et al (2007). Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nat Cell Biol, 9, 316-23. https://doi.org/10.1038/ncb1547
  32. Wang W, Wang H, Rayburn ER, et al (2008). 20 (S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol, a novel natural product for prostate cancer therapy: activity in vitro and in vivo and mechanisms of action. Br J Cancer, 98, 792-802. https://doi.org/10.1038/sj.bjc.6604227
  33. Wang Z, Zheng Q, Liu K, et al (2006). Ginsenoside Rh (2) enhances antitumour activity and decreases genotoxic effect of cyclophosphamide. Basic Clin Pharmacol Toxicol, 98, 411-5. https://doi.org/10.1111/j.1742-7843.2006.pto_348.x
  34. Wullschleger S, Loewith R, Hall MN (2006). TOR signaling in growth and metabolism. Cell, 124, 471-84. https://doi.org/10.1016/j.cell.2006.01.016
  35. Xu W, Seiter K, Feldman E, et al (1996). The differentiation and maturation mediator for human myeloid leukemia cells shares homology with neuroleukin or phosphoglucose isomerase. Blood, 87, 4502-6.
  36. Yakirevich E, Naot Y (2000). Cloning of a glucose phosphate isomerase/neuroleukin-like sperm antigen involved in sperm agglutination. Biol Reprod, 62, 1016-23. https://doi.org/10.1095/biolreprod62.4.1016
  37. Yanagawa T, Funasaka T, Tsutsumi S, et al (2004). Novel roles of the autocrine motility factor/phosphoglucose isomerase in tumor malignancy. Endocr Relat Cancer, 11, 749-59. https://doi.org/10.1677/erc.1.00811
  38. Zhang C, Yu H, Hou J (2011). Effects of 20 (S) -ginsenoside Rh2 and 20 (R) -ginsenoside Rh2 on proliferation and apoptosis of human lung adenocarcinoma A549 cells. Zhongguo Zhong Yao Za Zhi, 36, 1670-4.

Cited by

  1. Proliferative and Inhibitory Activity of Siberian ginseng (Eleutherococcus senticosus) Extract on Cancer Cell Lines; A-549, XWLC-05, HCT-116, CNE and Beas-2b vol.16, pp.11, 2015, https://doi.org/10.7314/APJCP.2015.16.11.4781
  2. How do glycolytic enzymes favour cancer cell proliferation by nonmetabolic functions? vol.34, pp.29, 2015, https://doi.org/10.1038/onc.2014.320
  3. 20(S)-Ginsenoside Rh2 Induce the Apoptosis and Autophagy in U937 and K562 Cells vol.10, pp.3, 2018, https://doi.org/10.3390/nu10030328