Skip to main content
Log in

Caudatin induces cell cycle arrest and caspase-dependent apoptosis in HepG2 cell

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

In the present study, we investigate the anti-cancer activity and mechanism of caudatin, the C-21 steroidal glycosides, on human hepatoma cell line HepG2. The MTT assay and flow cytometry were used to evaluate HepG2 cell proliferation and cell cycle. Annexin-V/PI and DAPI staining were used to investigate cell apoptosis. Western blotting analysis was used to evaluate the expression levels of proteins. It is found that caudatin inhibits HepG2 cell growth and induces of G0/G1 phase arrest in a dose dependent manner, which is associated with a decreased in the expression of cyclinD1 and increased the levels of p21 and p53. HepG2 cells dealing with caudatin showed typical characteristics of apoptosis. Western blotting analysis indicated that the levels of Bcl-2 were down-regulated after caudatin treatment, whereas the expression of Bax was up-regulated. Furthermore, caudatin-induced apoptosis was accompanied by activation of caspase-3, -9, and poly(ADP-Ribose) Polymerase (PARP). Treatment with caudatin also induced phosphorylation of extracellular-signal regulating kinase (ERK) and c-Jun N-terminal kinase (JNK). These results demonstrate that caudatin inhibits cell proliferation via DNA synthesis reduction and induces caspase-dependent apoptosis in HepG2 cell. Activation of ERK and JNK may be involved in caudatin-induced hepatoma cell apoptosis.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  2. Charette N, De Saeger C, Lannoy V, Horsmans Y, Leclercq I, Starkel P (2010) Salirasib inhibits the growth of hepatocarcinoma cell lines in vitro and tumor growth in vivo through ras and mTOR inhibition. Mol Cancer 9:256. doi:10.1186/1476-4598-9-256

  3. Su M, Wu X, Chung HY, Li Y, Ye W (2009) Antiproliferative activities of five Chinese medicinal herbs and active compounds in Elephantopus scaber. Nat Prod Commun 4:1025–1030

    PubMed  CAS  Google Scholar 

  4. Chang C, Zhu Y, Tang X, Tao W (2010) The anti-proliferative effects of norcantharidin on human HepG2 cells in cell culture. Mol Biol Rep. doi:10.1007/s11033-010-0090-6

  5. Zhang R, Liu Y, Wang Y, Ye Y, Li X (2007) Cytotoxic and apoptosis-inducing properties of auriculoside A in tumor cells. Chem Biodivers 4:887–892. doi:10.1002/cbdv.200790076

    Article  PubMed  CAS  Google Scholar 

  6. Peng YR, Li YB, Liu XD, ZhangJF Duan JA (2008) Apoptosis induced by caudatin in human hepatoma cell line SMMC7721. Chin J Nat Med 6:210–213

    Article  CAS  Google Scholar 

  7. Brunelle JK, Letai A (2009) Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci 122:437–441. doi:10.1242/jcs.031682

    Article  PubMed  CAS  Google Scholar 

  8. Zhu J, Zhang L, Jin X, Han X, Sun C, Yan J (2010) beta-Ionone-induced apoptosis in human osteosarcoma (U2os) cells occurs via a p53-dependent signaling pathway. Mol Biol Rep 37:2653–2663. doi:10.1007/s11033-009-9793-y

    Article  PubMed  CAS  Google Scholar 

  9. Jarpe MB, Widmann C, Knall C, Schlesinger TK, Gibson S, Yujiri T, Fanger GR, Gelfand EW, Johnson GL (1998) Anti-apoptotic versus pro-apoptotic signal transduction: checkpoints and stop signs along the road to death. Oncogene 17:1475–1482. doi:10.1038/sj.onc.1202183

    Article  PubMed  CAS  Google Scholar 

  10. Yuen MF, Hou JL, Chutaputti A (2009) Asia Pacific working party on prevention of hepatocellular carcinoma hepatocellular carcinoma in the Asia pacific region. J Gastroenterol Hepatol 24:346–353. doi:10.1111/j.1440-1746.2009.05784.x

    Article  PubMed  Google Scholar 

  11. Xiao D, Herman-Antosiewicz A, Antosiewicz J, Xiao H, Brisson M, Lazo JS, Singh SV (2005) Diallyl trisulfide-induced G(2)-M phase cell cycle arrest in human prostate cancer cells is caused by reactive oxygen species-dependent destruction and hyperphosphorylation of Cdc 25 C. Oncogene 24:6256–6268. doi:10.1038/sj.onc.1208759

    Article  PubMed  CAS  Google Scholar 

  12. Alfonso LF, Srivenugopal KS, Arumugam TV, Abbruscato TJ, Weidanz JA, Bhat GJ (2009) Aspirin inhibits camptothecin-induced p21CIP1 levels and potentiates apoptosis in human breast cancer cells. Int J Oncol 34:597–608

    PubMed  CAS  Google Scholar 

  13. Singh SV, Herman-Antosiewicz A, Singh AV, Lew KL, Srivastava SK, Kamath R, Brown KD, Zhang L, Baskaran R (2004) Sulforaphaneinduced G2/M phase cell cycle arrest involves checkpoint kinase 2 mediated phosphorylation of Cdc25C. J Biol Chem 279:25813–25822. doi:10.1074/jbc.M313538200

    Article  PubMed  CAS  Google Scholar 

  14. Lapenna S, Giordano A (2009) Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov 8:547–566. doi:10.1038/nrd2907

    Article  PubMed  CAS  Google Scholar 

  15. Satyanarayana A, Kaldis P (2009) Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms. Oncogene 28:2925–2939. doi:10.1038/onc.2009.170

    Article  PubMed  CAS  Google Scholar 

  16. Heath-Engel HM, Chang NC, Shore GC (2008) The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family. Oncogene 27:6419–6433. doi:10.1038/onc.2008.309

    Article  PubMed  CAS  Google Scholar 

  17. Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9:47–59. doi:10.1038/nrm2308

    Article  PubMed  CAS  Google Scholar 

  18. Kumar S (2007) Caspase function in programmed cell death. Cell Death Differ 14:32–43. doi:10.1038/sj.cdd.4402060

    Article  PubMed  CAS  Google Scholar 

  19. Allan LA, Clarke PR (2009) Apoptosis and autophagy: regulation of caspase-9 by phosphorylation. FEBS J 276:6063–6073. doi:10.1111/j.1742-4658.2009.07330.x

    Article  PubMed  CAS  Google Scholar 

  20. Yun SI, Yoon HY, Chung YS (2009) Glycogen synthase kinase-3beta regulates etoposide-induced apoptosis via Bcl-2 mediated caspase-3 activation in C3H10T1/2 cells. Apoptosis 14:771–777. doi:10.1007/s10495-009-0348-4

    Article  PubMed  CAS  Google Scholar 

  21. Droga-Mazovec G, Bojic L, Petelin A, Ivanova S, Romih R, Repnik U, Salvesen GS, Stoka V, Turk V, Turk B (2008) Cysteine cathepsins trigger caspase-dependent cell death through cleavage of bid and antiapoptotic Bcl-2 homologues. J Biol Chem 283:19140–19150. doi:10.1074/jbc.M802513200

    Article  PubMed  CAS  Google Scholar 

  22. Wagner EF, Nebreda AR (2009) Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 9:537–549. doi:10.1038/nrc2694

    Article  PubMed  CAS  Google Scholar 

  23. Xie P, Guo S, Fan Y, Zhang H, Gu D, Li H (2009) Atrogin-1/MAFbx enhances simulated ischemia/reperfusion-induced apoptosis in cardiomyocytes through degradation of MAPK phosphatase-1 and sustained JNK activation. J Biol Chem 284:5488–5496. doi:10.1074/jbc.M806487200

    Article  PubMed  CAS  Google Scholar 

  24. Chen YS, Li HR, Lin M, Chen G, Xie BS, Xu NL, Lin LF (2010) Livin abrogates apoptosis of SPC-A1 cell by regulating JNKI signaling pathway. Mol Biol Rep 37:2241–2247. doi:10.1007/s11033-009-9711-3

    Article  PubMed  CAS  Google Scholar 

  25. Milne DM, Campbell DG, Caudwell FB, Meek DW (1994) Phosphorylation of the tumor suppressor protein p53 by mitogen-activated protein kinases. J Biol Chem 269:9253–9260

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No 30800422).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Feng Ze Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fei, H.R., Chen, H.L., Xiao, T. et al. Caudatin induces cell cycle arrest and caspase-dependent apoptosis in HepG2 cell. Mol Biol Rep 39, 131–138 (2012). https://doi.org/10.1007/s11033-011-0721-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-011-0721-6

Keywords

Navigation