Biotechnology and Bioprocess Engineering

, Volume 24, Issue 3, pp 560–567 | Cite as

6-shogaol a Active Component from Ginger Inhibits Cell Proliferation and Induces Apoptosis through Inhibition of STAT-3 Translocation in Ovarian Cancer Cell Lines (A2780)

  • Ting Liang
  • Ying He
  • Yuhua Chang
  • Xiantong LiuEmail author
Research Paper


Ovarian cancer is predominant form of malignant which occupies 70 % cancer in women worldwide. Taxals, anthrocyclins and platinum based drugs are used as chemotherapeutic for treatment of ovarian cancer. These drugs were limited by drug resistance and it produces several toxicity. Therefore, we used natural drug which inhibits the cancer cell growth by modulating specific molecular mechanisms. This study, we evaluated the 6-shogaol a active component from ginger inhibits cell proliferation by modulation of JAK/STAT-3 signalling in ovarian cancer cell lines (A2780). In this study, we found that 6-shogaol induces cytotoxicity, ROS production and apoptosis in A2780 cell lines by time depending manner. Moreover, signal transducer and activating transcription-3 (STAT-3) has been consider as novel transcriptional factor which regulates apoptosis, cell proliferation and angiogensis. Inhibition of STAT-3 transcription considered as novel strategy to inhibiting ovarian cell growth. In this study, we found that 6-shogaol inhibits STAT-3 translocation there by inhibits the over expression of PCNA, cyclin-D1, Bcl-2 and decreased expression of Bax, caspase-9 and 3 in A2780 cell lines. This results concluded that 6-shogaol inhibits ovarian cell growth and induces apoptosis through inhibits the translocation STAT-3.


6-shogaol ovarian cancer apoptosis STAT-3 


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  1. 1.
    Wang, Y., L. Li, and X. Guo, (2012) Interleukin-6 signaling regulates anchorage-independent growth, proliferation, adhesion and invasion in human ovarian cancer cells. Cytokine 59: 228–236.CrossRefGoogle Scholar
  2. 2.
    Rath, K. S., H. M. Funk, M. C. Bowling, W. F. Richards, and A. F. Drew (2010) Expression of soluble interleukin-6 receptor in malignant ovarian tissue. Am. J. Obstet. Gynecol. 203: 230. e1–e8.CrossRefGoogle Scholar
  3. 3.
    Saini, U., S. Naidu, and A. C. ElNaggar (2017) Elevated STAT3 expression in ovarian cancer ascites promotes invasion and metastasis: a potential therapeutic target. Oncogene 36: 168–181.CrossRefGoogle Scholar
  4. 4.
    Siegel, R. L., K. D. Miller, and A. Jemal (2016) Cancer statistics, CA Cancer J. Clin. 66: 7–30.CrossRefGoogle Scholar
  5. 5.
    Debashis and Nath (2018) Ovarian Cancer - The Silent Killer. J. Tumor. Res. 3: 3.Google Scholar
  6. 6.
    Siegel, R. L., K. D. Miller, and A. Jemal (2018) Cancer statistics, 2018.Google Scholar
  7. 7.
    Rubin, S. C., T. C. Randall, K. A. Armstrong, D. S. Chi, and W. J. Hoskins (1999) Ten-year follow-up of ovarian cancer patients after second-look laparotomy with negative findings. Obstet. Gynecol. 93: 21–24.Google Scholar
  8. 8.
    Kowshik, J., A. B. Baba, H. Giri, G. D. Reddy, M. Dixit, and S. Nagini S (2014) Astaxanthin inhibits JAK/STAT-3 signaling to abrogate cell proliferation, invasion and angiogenesis in a hamster model of oral cancer. PLoS One 8. 9: e109114.Google Scholar
  9. 9.
    Taub, R. (2003) Hepatoprotection via the IL-6/Stat3 pathway. J. Clin. Invest. 112: 978–980.CrossRefGoogle Scholar
  10. 10.
    Mishra, R. and B. R. Das (2009) Cyclin D1 expression and its possible regulation in chewing tobacco mediated oral squamous cell carcinoma progression. Arch. Oral. Biol. 54: 917–923.CrossRefGoogle Scholar
  11. 11.
    Balupillai, A., N. R. Prasad, K. Ramasamy, and G. Muthusamy (2015) Caffeic acid inhibits UVB-induced inflammation and photocarcinogenesis through activation of peroxisome proliferator-activated receptor-γ in mouse skin. Photochem. Photobiol. 91: 1458–68.CrossRefGoogle Scholar
  12. 12.
    Oltvai, Z. N., C. L. Milliman, and S. J. Korsmeyer (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74: 609–619.CrossRefGoogle Scholar
  13. 13.
    Wang, S. W. and Y. M. Sun (2014) The IL-6/JAK/STAT3 pathway: potential therapeutic strategies in treating colorectal cancer. International Journal of Oncology 2 Apr 1. 44: 1032–40.CrossRefGoogle Scholar
  14. 14.
    Garcia, R., T. L. Bowman, and G. Niu, (2001) Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene 20: 2499–2513.CrossRefGoogle Scholar
  15. 15.
    Spices Board (2011) Spices Board of India. Accessed 1 Aug 2011
  16. 16.
    Suekawa, M., A. Ishige, K. Yuasa, K. Sudo, M. Aburada, and E. Hosoya (1984) Pharmacological studies on ginger. I. Pharmacological actions of pungent constitutents, (6)-gingerol and (6)-shogaol. J. Pharmacobiodyn. 7: 836–848.CrossRefGoogle Scholar
  17. 17.
    Pan, M. H., M. C. Hsieh, J. M. Kuo, C. S. Lai, H. Wu, S. Sang, and C. T. Ho (2008) 6-Shogaol induces apoptosis in human colorectal carcinoma cells via ROS production, caspase activation, and GADD 153 expression. Mol. Nutr. Food Res. 52: 527–37.CrossRefGoogle Scholar
  18. 18.
    Pan, M. H., M. C. Hsieh, P. C. Hsu, S. Y. Ho, C. S. Lai, and H. Wu (2008a) 6-Shogaol suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages. Mol. Nutr. Food Res. 52: 1467–1477.CrossRefGoogle Scholar
  19. 19.
    Gunaseelan, S., A. Balupillai, K. Govindasamy, G Muthusamy, K. Ramasamy, M. Shanmugam, and N. R. Prasad (2016) The preventive effect of linalool on acute and chronic UVB-mediated skin carcinogenesis in Swiss albino mice. Photochem. Photobiol. Sci. 15: 851–60.CrossRefGoogle Scholar
  20. 20.
    Balupillai, A., R. P. Nagarajan, K. Ramasamy, K. Govindasamy, and G. Muthusamy (2018) Caffeic acid prevents UVB radiation induced photocarcinogenesis through regulation of PTEN signaling in human dermal fibroblasts and mouse skin. Toxicol. Appl. Pharmacol. 352: 87–96.CrossRefGoogle Scholar
  21. 21.
    Ovarian Cancer Statistics, 2018 C.A: A Cancer J for Clindoi:
  22. 22.
    SEER Cancer Statistics Factsheets: Ovary Cancer. National Cancer Institute. Bethesda, MDGoogle Scholar
  23. 23.
    Alagkiozidis, I., A. Facciabene, and M. Tsiatas (2011) Time-dependent cytotoxic drugs selectively cooperate with IL-18 for cancer chemo-immunotherapy. J. Transl. Med. 9: 77.CrossRefGoogle Scholar
  24. 24.
    Pashaei-Asl, R., F. Pashaei-Asl, and P. MostafaGharabaghi (2017) The inhibitory effect of ginger extract on ovarian cancer cell line; application of systems biology. Adv. Pharm. Bull. 7: 241–249.CrossRefGoogle Scholar
  25. 25.
    Lokeshkumar, B., V. Sathishkumar, N. Nandakumar, T. Rengarajan, A. Madankumar, and M. P. Balasubramanian (2015) Anti-oxidative effect of myrtenal in prevention and treatment of colon cancer induced by 1, 2-dimethyl hydrazine (dmh) in experimental animals. Biomol. Ther. 23: 471.CrossRefGoogle Scholar
  26. 26.
    Liu, Y., L. Tong, Y. Luo, X. Li, G. Chen, and Y. Wang (2018) Resveratrol inhibits the proliferation and induces the apoptosis in ovarian cancer cells via inhibiting glycolysis and targeting AMPK/mTOR signaling pathway. J. Cell Biochem. 119: 6162–6172.CrossRefGoogle Scholar
  27. 27.
    Annamalai G., S. Kathiresan, and N. Kannappan (2016) [6]-Shogaol, a dietary phenolic compound, induces oxidative stress mediated mitochondrial dependant apoptosis through activation of proapoptotic factors in Hep-2 cells. Biomed. Pharmacother. 82: 226–36.CrossRefGoogle Scholar
  28. 28.
    Leone, A., M. S. Roca, C. Ciardiello, S. Costantini, and A. Budillon (2017) Oxidative stress gene expression profile correlates with cancer patient poor prognosis: identification of crucial pathways might select novel therapeutic approaches. Oxid. Med. Cell Longev. 2017: 2597581.CrossRefGoogle Scholar
  29. 29.
    Shi, F., F. F. Cai, and L. Cai (2017) Overexpression of SYF2 promotes cell proliferation and correlates with poor prognosis in human breast cancer. Oncotarget 8: 88453–88463.Google Scholar
  30. 30.
    Amanda L. Rinkenbaughand and Albert S. Baldwin (2016) The NF-αB pathway and cancer stem cells. Cells 5: 16.CrossRefGoogle Scholar
  31. 31.
    Wolter, F., B. Akoglu, A. Clausnitzer, and J. Stein (2001) Downregulation of the cyclin D1/Cdk4 complex occurs during resveratrol-induced cell cycle arrest in colon cancer cell lines. J. Nutr. 131: 2197–203.CrossRefGoogle Scholar
  32. 32.
    Hong, F., B. Jaruga, W. H. Kim, S. Radaeva, O. N. El-Assal, Z. Tian, V. A. Nguyen, and B. Gao (2002) Opposing roles of STAT1 and STAT3 in T cell-mediated hepatitis: Regulation by SOCS. J. Clin. Investig. 110: 1503–1513.CrossRefGoogle Scholar
  33. 33.
    Lai, K. O., Y. Chen, H. M. Po, K. G. Lok, K. Gong, and N. Y. Ip (2004) Identification of the Jak/Stat proteins as novel downstream targets of EphA4 signaling in muscle: implications in the regulation of acetylcholinesterase expression. J. Biol. Chem. 279: 13383–92.CrossRefGoogle Scholar
  34. 34.
    Agilan, B., N. Rajendra Prasad, G. Kanimozhi, R. Karthikeyan, M. Ganesan, S. Mohana, and D. Ananthakrishnan (2016) Caffeic acid inhibits chronic UVB-induced cellular proliferation through JAK-STAT 3 signaling in mouse skin. Photochem. Photobiol. 92: 467–74.CrossRefGoogle Scholar
  35. 35.
    Maryam, A., T. Mehmood, H. Zhang, Y. Li, M. Khan, and T. Ma (2017) Alantolactone induces apoptosis, promotes STAT3 glutathionylation and enhances chemosensitivity of A549 lung adenocarcinoma cells to doxorubicin via oxidative stress. Sci. Rep. 7: 6242.CrossRefGoogle Scholar
  36. 36.
    Saxton, R. A. and D. M. Sabatini (2017) mTOR signaling in growth, metabolism, and disease. Cell 168: 960–76.CrossRefGoogle Scholar
  37. 37.
    Yang, D., X. Zhang, W. Zhang, and T. Rengarajan (2018) Vicenin-2 inhibits Wnt/β-catenin signaling and induces apoptosis in HT-29 human colon cancer cell line. Drug Design, Devel Ther. 12: 1303.CrossRefGoogle Scholar
  38. 38.
    Liu, Q., Y. B. Peng, P. Zhou, L. W. Qi, et al. (2013). 6-Shogaol induces apoptosis in human leukemia cells through a process involving caspase-mediated cleavage of eIF2α. Mol. Cancer 12: 135.CrossRefGoogle Scholar
  39. 39.
    Ling, H., H. Yang, S. H. Tan, W. K. Chui, and E. H. Chew (2010) 6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-κB activation. Br. J. Pharmacol. 161: 1763–77.CrossRefGoogle Scholar

Copyright information

© The Korean Society for Biotechnology and Bioengineering and Springer 2019

Authors and Affiliations

  • Ting Liang
    • 1
  • Ying He
    • 2
  • Yuhua Chang
    • 3
  • Xiantong Liu
    • 3
    Email author
  1. 1.Biomedical Isotope Research Center, School of Basic Medical SciencesShandong UniversityJinan, Shandong ShandongChina
  2. 2.Department of Gynaecology and ObstetricsFeixian People’s HospitalLinyi, ShandongChina
  3. 3.Maternal and Child Health Care of Shandong ProvinceJinan, ShandongChina

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