Skip to main content

Advertisement

Log in

Peroxiredoxin 3 is resistant to oxidation-induced apoptosis of Hep-3b cells

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Objective

Although peroxiredoxin 3 (PRX3) was reported to be overexpressed in liver cancer, the precise function of PRX3 in the development and/or progression of liver cancer remained to be obscure. The present study was conducted to investigate the response of PRX3 to oxidative stress in hepatocellular carcinoma (HCC) cells.

Methods

After successful knockdown of PRX3 expression by small interfering RNA, we treated HCC cell lines Hep-3b and Hep-G2 with gradient concentrations of H2O2 and detected cell proliferation, apoptosis, and the level of reactive oxygen species (ROS) in the cells.

Results

After low-dose (5–20 μmol/l) H2O2 treatment, the ROS level was significantly higher in PRX3-knockdown Hep-3b cells than in controls. In addition, PRX3 down-regulation resulted in decreased proliferation, increased apoptosis, and increased caspase 3 activity of Hep-3b cells. We did not notice significant difference between PrxIII knockdown and control Hep-G2 cells in ROS level, cell viability or apoptosis.

Conclusion

Our results suggest that PRX3 is an indispensable ROS scavenger that protects tumor cells against oxidative damage and subsequent apoptosis, which provides a clue that PRX3 may be involved in the chemotherapeutic resistance of liver cancer. The underlying mechanism for PRX3 function needs further investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. World Health Organization. Global alert and response (GAR). In: Hepatitis B: surveillance and control. 2009. http://www.who.int/csr/disease/hepatitis/whocdscsrlyo20022/en/index4.html. Accessed 23 Oct 2009.

  2. Lu FM, Zhuang H. Management of hepatitis B in China. Chin Med J (Engl). 2009;122:3–4.

    PubMed  Google Scholar 

  3. Song P, Feng X, Zhang K, Song T, Ma K, Kokudo N, et al. Screening for and surveillance of high-risk patients with HBV-related chronic liver disease: promoting the early detection of hepatocellular carcinoma in China. Biosci Trends. 2013;7:1–6.

    PubMed  Google Scholar 

  4. Yeh CT, Chen HC, Sung CM, Hsu CL, Lin CC, Pan KT, et al. Retrospective comparison between a regular and a split-dose protocol of 5-fluorouracil, cisplatin, and mitoxantrone for the treatment of far advanced hepatocellular carcinoma. BMC Cancer. 2011;11:117.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Zhang ZM, Guo JX, Zhang ZC, Jiang N, Zhang ZY, Pan LJ. Therapeutic options for intermediate-advanced hepatocellular carcinoma. World J Gastroenterol. 2011;17:1685–9.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Srinivas P, Gopinath G, Banerji A, Dinakar A, Srinivas G. Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells. Mol Carcinog. 2004;40:201–11.

    Article  CAS  PubMed  Google Scholar 

  7. Alexandre J, Batteux F, Nicco C, Chéreau C, Laurent A, Guillevin L, et al. Accumulation of hydrogen peroxide is an early and crucial step for paclitaxel-induced cancer cell death both in vitro and in vivo. Int J Cancer. 2006;119:41–8.

    Article  CAS  PubMed  Google Scholar 

  8. Chung YM, Yoo YD, Park JK, Kim YT, Kim HJ. Increased expression of peroxiredoxin II confers resistance to cisplatin. Anticancer Res. 2001;21:1129–33.

    CAS  PubMed  Google Scholar 

  9. Zhang B, Su Y, Ai G, Wang Y, Wang T, Wang F. Involvement of peroxiredoxin I in protecting cells from radiation-induced death. J Radiat Res (Tokyo). 2005;46:305–12.

    Article  CAS  Google Scholar 

  10. Wang T, Tamae D, LeBon T. The role of peroxiredoxin II in radiation-resistant MCF-7 breast cancer cells. Cancer Res. 2005;65:10338–46.

    Article  CAS  PubMed  Google Scholar 

  11. Watabe S, Hiroi T, Yamamoto Y, Fujioka Y, Hasegawa H, Yago N, et al. SP-22 is a thioredoxin-dependent peroxide reductase in mitochondria. Eur J Biochem. 1997;249:52–60.

    Article  CAS  PubMed  Google Scholar 

  12. Chae HZ, Kim HJ, Kang SW, Rhee SG. Characterization of three isoforms of mammalian peroxiredoxin that reduce peroxides in the presence of thioredoxin. Diabetes Res Clin Pract. 1999;45:101–12.

    Article  CAS  PubMed  Google Scholar 

  13. Chang TS, Cho CS, Park S. Peroxiredoxin III, a mitochondrion-specific peroxidase, regulates apoptotic signaling by mitochondria. J Biol Chem. 2004;279:41975–84.

    Article  CAS  PubMed  Google Scholar 

  14. Nonn L, Berggren M, Powis G. Increased expression of mitochondrial peroxiredoxin-3 (thioredoxin peroxidase-2) protects cancer cells against hypoxia and drug-induced hydrogen peroxide-dependent apoptosis. Mol Cancer Res. 2003;1:682–9.

    CAS  PubMed  Google Scholar 

  15. Chua PJ, Lee EH, Yu Y, Yip GW, Tan PH, Bay BH. Silencing the Peroxiredoxin III gene inhibits cell proliferation in breast cancer. Int J Oncol. 2010;36:359–64.

    CAS  PubMed  Google Scholar 

  16. Duan J, Lang Y, Song C, Xiong J, Wang Y, Yan Y. siRNA targeting of PRDX3 enhances cisplatin-induced apoptosis in ovarian cancer cells through the suppression of the NF-κB signaling pathway. Mol Med Rep. 2013;7:1688–94.

    CAS  PubMed  Google Scholar 

  17. Li L, Kaifu T, Obinata M, Takai T. Peroxiredoxin III-deficiency sensitizes macrophages to oxidative stress. J Biochem. 2009;145:425–7.

    Article  CAS  PubMed  Google Scholar 

  18. Shih SF, Wu YH, Hung CH, Yang HY, Lin JY. Abrin triggers cell death by inactivating a thiol-specific antioxidant protein. J Biol Chem. 2001;276:21870–7.

    Article  CAS  PubMed  Google Scholar 

  19. Wang XY, Wang HJ, Li XQ. Peroxiredoxin III protein expression is associated with platinum resistance in epithelial ovarian cancer. Tumour Biol. 2013;34:2275–81.

    Article  CAS  PubMed  Google Scholar 

  20. Whitaker HC, Patel D, Howat WJ, Warren AY, Kay JD, Sangan T, et al. Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress. Br J Cancer. 2013. doi:10.1038/bjc.2013.396.

    PubMed  Google Scholar 

  21. Choi JH, Kim TN, Kim S. Overexpression of mitochondrial thioredoxin reductase and peroxiredoxin III in hepatocellular carcinomas. Anticancer Res. 2002;22:3331–5.

    CAS  PubMed  Google Scholar 

  22. Qiao B, Wang J, Xie J, Niu Y, Ye S, Wan Q, et al. Detection and identification of peroxiredoxin 3 as a biomarker in hepatocellular carcinoma by a proteomic approach. Int J Mol Med. 2012;29:832–40.

    CAS  PubMed  Google Scholar 

  23. Li L, Zhang YG, Chen CL. Anti-apoptotic role of peroxiredoxin III in cervical cancer cells. FEBS Open Bio. 2013;3:51–4.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Shibata E, Nanri H, Ejima K, Araki M, Fukuda J, Yoshimura K, et al. Enhancement of mitochondrial oxidative stress and up-regulation of antioxidant protein peroxiredoxin III/SP-22 in the mitochondria of human pre-eclamptic placentae. Placenta. 2003;24:698–705.

    Article  CAS  PubMed  Google Scholar 

  25. Li L, Shoji W, Oshima H, Obinata M, Fukumoto M, Kanno N. Crucial role of peroxiredoxin III in placental antioxidant defense of mice. FEBS Lett. 2008;582:2431–4.

    Article  CAS  PubMed  Google Scholar 

  26. Shen C, Nathan C. Nonredundant antioxidant defense by multiple two-cysteine peroxiredoxins in human prostate cancer cells. Mol Med. 2002;8:95–102.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Karihtala P, Mäntyniemi A, Kang SW, Kinnula VL, Soini Y. Peroxiredoxins in breast carcinoma. Clin Cancer Res. 2003;9:3418–24.

    CAS  PubMed  Google Scholar 

  28. Park JH, Kim YS, Lee HL, Shim JY, Lee KS, Oh YJ, et al. Expression of peroxiredoxin and thioredoxin in human lung cancer and paired normal lung. Respirology. 2006;11:269–75.

    Article  PubMed  Google Scholar 

  29. Wu XY, Fu ZX, Wang XH. Peroxiredoxins in colorectal neoplasms. Histol Histopathol. 2010;25:1297–303.

    CAS  PubMed  Google Scholar 

  30. Safaeian M, Hildesheim A, Gonzalez P, Yu K, Porras C, Li Q, et al. Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer. PLoS ONE. 2012;7:e33619.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that there is no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, YG., Li, L., Liu, CH. et al. Peroxiredoxin 3 is resistant to oxidation-induced apoptosis of Hep-3b cells. Clin Transl Oncol 16, 561–566 (2014). https://doi.org/10.1007/s12094-013-1117-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-013-1117-y

Keywords

Navigation