Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
September-2016 Volume 14 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2016 Volume 14 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Inhibition of multiple myeloma cell proliferation by ginsenoside Rg3 via reduction in the secretion of IGF-1

  • Authors:
    • Yan Li
    • Tao Yang
    • Jing Li
    • Hong‑Ling Hao
    • Su‑Yun Wang
    • Jie Yang
    • Jian‑Min Luo
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, The Second Hospital, Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Urinary Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China, Department of Hematology, Hebei Province Chinese Medicine Hospital, Shijiazhuang, Hebei 050011, P.R. China, Department of Hematology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
  • Pages: 2222-2230
    |
    Published online on: July 7, 2016
       https://doi.org/10.3892/mmr.2016.5475
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Ginsenoside Rg3 (Rg3) is one of the primary constituents isolated from ginseng, and has been found to exhibit cytotoxic effects against cancer cells. The present study aimed to investigate the effects of Rg3 on human multiple myeloma cell proliferation and apoptosis, and to examine its underlying molecular mechanisms. Cell viability was detected using a Cell Counting kit‑8 assay, and cell cycle arrest and cell apoptosis were analyzed using flow cytometry. In addition, the expression levels of cell cycle‑associated markers and apoptosis‑associated proteins, and the release of cytochrome C were determined using western blot analysis. The effects of Rg3 on the insulin‑like growth factor (IGF)-1/AKT/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase signaling pathways were also investigated using western blot analysis. The results showed that Rg3 inhibited cell viability in U266, RPMI8226 and SKO‑007 cells in a time‑ and dose‑dependent manner, and caused cell cycle arrest in the G1 phase by regulating the cyclin‑dependent kinase pathway. Furthermore, Rg3 induced multiple myeloma cell apoptosis, and was involved in B cell lymphoma-2 (Bcl2)/Bcl2-associated X protein imbalance, caspase activation and the release of cytochrome C from the mitochondria into the cytoplasm. Mechanistically, it was found that the inhibitory effects of Rg3 on multiple myeloma cell proliferation were essential for secretion of IGF‑1 and inactivation of the Akt/mTOR pathway. Collectively, these findings demonstrated that Rg3 effectively inhibited cell proliferation and induced apoptosis of multiple myeloma cells. These data broaden the clinical investigation of Rg3 in the treatment of multiple myeloma, associated with the inactivation of IGF-1/AKT/mTOR signaling.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Raab MS, Podar K, Breitkreutz I, Richardson PG and Anderson KC: Multiple myeloma. Lancet. 374:324–339. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Di Martino MT, Gullà A, Cantafio ME, Lionetti M, Leone E, Amodio N, Guzzi PH, Foresta U, Conforti F, Cannataro M, et al: In vitro and in vivo anti-tumor activity of miR-221/222 inhibitors in multiple myeloma. Oncotarget. 4:242–255. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Huang EW, Xue SJ, Li XY, Xu SW, Cheng JD, Zheng JX, Shi H, Lv GL, Li ZG, Li Y, et al: EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion. Biochem Biophys Res Commun. 447:271–277. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Kumar S and Rajkumar SV: Thalidomide and lenalidomide in the treatment of multiple myeloma. Eur J Cancer. 42:1612–1622. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Kyle RA and Rajkumar SV: Multiple myeloma. Blood. 111:2962–2972. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Richardson PG, Mitsiades C, Schlossman R, Ghobrial I, Hideshima T, Munshi N and Anderson KC: Bortezomib in the front-line treatment of multiple myeloma. Expert Rev Anticancer Ther. 8:1053–1072. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Hideshima T, Chauhan D, Shima Y, Raje N, Davies FE, Tai YT, Treon SP, Lin B, Schlossman RL, Richardson P, et al: Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood. 96:2943–2950. 2000.PubMed/NCBI

8 

Brown RE, Stern S, Dhanasiri S and Schey S: Lenalidomide for multiple myeloma: Cost-effectiveness in patients with one prior therapy in England and Wales. Eur J Health Econ. 14:507–514. 2013. View Article : Google Scholar

9 

Lee JY, Jung KH, Morgan MJ, Kang YR, Lee HS, Koo GB, Hong SS, Kwon SW and Kim YS: 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

10 

Park EH, Kim YJ, Yamabe N, Park SH, Kim HK, Jang HJ, Kim JH, Cheon GJ, Ham J and Kang KS: Stereospecific anticancer effects of ginsenoside Rg3 epimers isolated from heat-processed American ginseng on human gastric cancer cell. J Ginseng Res. 38:22–27. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Yuan HD, Quan HY, Zhang Y, Kim SH and Chung SH: 20(S)-Ginsenoside Rg3-induced apoptosis in HT-29 colon cancer cells is associated with AMPK signaling pathway. Mol Med Rep. 3:825–831. 2010.

12 

Min JK, Kim JH, Cho YL, Maeng YS, Lee SJ, Pyun BJ, Kim YM, Park JH and Kwon YG: 20(S)-Ginsenoside Rg3 prevents endothelial cell apoptosis via inhibition of a mitochondrial caspase pathway. Biochem Biophys Res Commun. 349:987–994. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Shan X, Fu YS, Aziz F, Wang XQ, Yan Q and Liu JW: Ginsenoside Rg3 inhibits melanoma cell proliferation through down-regulation of histone deacetylase 3 (HDAC3) and increase of p53 acetylation. PLoS One. 9:e1154012014. View Article : Google Scholar : PubMed/NCBI

14 

Kim BM, Kim DH, Park JH, Surh YJ and Na HK: Ginsenoside Rg3 inhibits constitutive activation of NF-kB signaling in human breast cancer (MDA-MB-231) cells: ERK and Akt as potential upstream targets. J Cancer Prev. 19:23–30. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Zeng D, Wang J, Kong P, Chang C and Li J and Li J: Ginsenoside Rg3 inhibits HIF-1α and VEGF expression in patient with acute leukemia via inhibiting the activation of PI3K/Akt and ERK1/2 pathways. Int J Clin Exp Pathol. 7:2172–2178. 2014.

16 

Sin S, Kim SY and Kim SS: Chronic treatment with ginsenoside Rg3 induces Akt-dependent senescence in human glioma cells. Int J Oncol. 41:1669–1674. 2012.PubMed/NCBI

17 

Jiang JW, Chen XM, Chen XH and Zheng SS: Ginsenoside Rg3 inhibit hepatocellular carcinoma growth via intrinsic apoptotic pathway. World J Gastroenterol. 17:3605–3613. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Sedding DG, Hermsen J, Seay U, Eickelberg O, Kummer W, Schwencke C, Strasser RH, Tillmanns H and Braun-Dullaeus RC: Caveolin-1 facilitates mechanosensitive protein kinase B (Akt) signaling in vitro and in vivo. Circ Res. 96:635–642. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Héron-Milhavet L, Franckhauser C, Rana V, Berthenet C, Fisher D, Hemmings BA, Fernandez A and Lamb NJ: Only Akt1 is required for proliferation, while Akt2 promotes cell cycle exit through p21 binding. Mol Cell Biol. 26:8267–8280. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Kuwabara I, Kuwabara Y, Yang RY, Schuler M, Green DR, Zuraw BL, Hsu DK and Liu FT: Galectin-7 (PIG1) exhibits pro-apoptotic function through JNK activation and mitochondrial cytochrome c release. J Biol Chem. 277:3487–3497. 2002. View Article : Google Scholar

21 

Cea M, Cagnetta A, Fulciniti M, Tai YT, Hideshima T, Chauhan D, Roccaro A, Sacco A, Calimeri T, Cottini F, et al: Targeting NAD+ salvage pathway induces autophagy in multiple myeloma cells via mTORC1 and extracellular signal-regulated kinase (ERK1/2) inhibition. Blood. 120:3519–3529. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, et al: RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 366:207–215. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Wajapeyee N, Serra RW, Zhu X, Mahalingam M and Green MR: Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell. 132:363–374. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Palazzolo I, Stack C, Kong L, Musaro A, Adachi H, Katsuno M, Sobue G, Taylor JP, Sumner CJ, Fischbeck KH and Pennuto M: Overexpression of IGF-1 in muscle attenuates disease in a mouse model of spinal and bulbar muscular atrophy. Neuron. 63:316–328. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Sun Y, Lin H, Zhu Y, Feng J, Chen Z, Li G, Zhang X, Zhang Z, Tang J, Shi M, et al: A randomized, prospective, multi-centre clinical trial of NP regimen (vinorelbine+cisplatin) plus Gensing Rg3 in the treatment of advanced non-small cell lung cancer patients. Zhongguo Fei Ai Za Zhi. 9:254–258. 2006.In Chinese. PubMed/NCBI

26 

Luo Y, Zhang P, Zeng HQ, Lou SF and Wang DX: Ginsenoside Rg3 induces apoptosis in human multiple myeloma cells via the activation of Bcl-2-associated X protein. Mol Med Rep. 12:3557–3562. 2015.PubMed/NCBI

27 

Song Y, Hou J, Kang L and Gao S: Effect of 20 (S)-ginsenoside Rg3 on the proliferation inhibition and secretion of vascular endothelial growth factor of multiple myeloma cell line U266. Zhonghua Xue Ye Xue Za Zhi. 35:519–523. 2014.In Chinese. PubMed/NCBI

28 

Woo RA and Poon RY: Cyclin-dependent kinases and S phase control in mammalian cells. Cell Cycle. 2:316–324. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Misiti F, Orsini F, Clementi ME, Lattanzi W, Giardina B and Michetti F: Mitochondrial oxygen consumption inhibition importance for TMT-dependent cell death in undifferentiated PC12 cells. Neurochem Int. 52:1092–1099. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Ott M, Gogvadze V, Orrenius S and Zhivotovsky B: Mitochondria, oxidative stress and cell death. Apoptosis. 12:913–922. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Mignotte B and Vayssiere JL: Mitochondria and apoptosis. Eur J Biochem. 252:1–15. 1998. View Article : Google Scholar : PubMed/NCBI

32 

Sharp ZD and Bartke A: Evidence for down-regulation of phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR)-dependent translation regulatory signaling pathways in Ames dwarf mice. J Gerontol A Biol Sci Med Sci. 60:293–300. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Morgensztern D and McLeod HL: PI3K/Akt/mTOR pathway as a target for cancer therapy. Anticancer Drugs. 16:797–803. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li Y, Yang T, Li J, Hao HL, Wang SY, Yang J and Luo JM: Inhibition of multiple myeloma cell proliferation by ginsenoside Rg3 via reduction in the secretion of IGF-1. Mol Med Rep 14: 2222-2230, 2016.
APA
Li, Y., Yang, T., Li, J., Hao, H., Wang, S., Yang, J., & Luo, J. (2016). Inhibition of multiple myeloma cell proliferation by ginsenoside Rg3 via reduction in the secretion of IGF-1. Molecular Medicine Reports, 14, 2222-2230. https://doi.org/10.3892/mmr.2016.5475
MLA
Li, Y., Yang, T., Li, J., Hao, H., Wang, S., Yang, J., Luo, J."Inhibition of multiple myeloma cell proliferation by ginsenoside Rg3 via reduction in the secretion of IGF-1". Molecular Medicine Reports 14.3 (2016): 2222-2230.
Chicago
Li, Y., Yang, T., Li, J., Hao, H., Wang, S., Yang, J., Luo, J."Inhibition of multiple myeloma cell proliferation by ginsenoside Rg3 via reduction in the secretion of IGF-1". Molecular Medicine Reports 14, no. 3 (2016): 2222-2230. https://doi.org/10.3892/mmr.2016.5475
Copy and paste a formatted citation
x
Spandidos Publications style
Li Y, Yang T, Li J, Hao HL, Wang SY, Yang J and Luo JM: Inhibition of multiple myeloma cell proliferation by ginsenoside Rg3 via reduction in the secretion of IGF-1. Mol Med Rep 14: 2222-2230, 2016.
APA
Li, Y., Yang, T., Li, J., Hao, H., Wang, S., Yang, J., & Luo, J. (2016). Inhibition of multiple myeloma cell proliferation by ginsenoside Rg3 via reduction in the secretion of IGF-1. Molecular Medicine Reports, 14, 2222-2230. https://doi.org/10.3892/mmr.2016.5475
MLA
Li, Y., Yang, T., Li, J., Hao, H., Wang, S., Yang, J., Luo, J."Inhibition of multiple myeloma cell proliferation by ginsenoside Rg3 via reduction in the secretion of IGF-1". Molecular Medicine Reports 14.3 (2016): 2222-2230.
Chicago
Li, Y., Yang, T., Li, J., Hao, H., Wang, S., Yang, J., Luo, J."Inhibition of multiple myeloma cell proliferation by ginsenoside Rg3 via reduction in the secretion of IGF-1". Molecular Medicine Reports 14, no. 3 (2016): 2222-2230. https://doi.org/10.3892/mmr.2016.5475
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team