Skip to main content
SpringerLink
Log in

PI3K/Akt pathway involving into apoptosis and invasion in human colon cancer cells LoVo

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

In this study we determined the effects of Curcumin on human colon cancer cells line LoVo. We found that Curcumin significantly inhibited the proliferation, migration and invasion, and clone formation of LoVo cells in a dose-dependent manner. Curcumin also dose-dependently reduced the phosphorylation of proteins Akt and increased expression levels of the genes caspase-3, cytochrome-c, Bax mRNA in LoVo cells. In addition, Curcumin dose-dependently decreased gene Bcl-2 mRNA expression. Similar results were observed in LoVo cells treated with LY294002. These in vitro studies suggest that Curcumin may play its anti-cancer actions partly via suppressing PI3K/Akt signal pathway in LoVo cells.

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

Access this article

Log in via an institution

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Boateng J, Verghese M, Shackelford L, Walker LT, Khatiwada J, Ogutu S, Williams DS, Jones J, Guyton M, Asiamah D, Henderson F, Grant L, DeBruce M, Johnson A, Washington S, Chawan CB (2007) Selected fruits reduce azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Food Chem Toxicol 45:725–732

    Article  CAS  PubMed  Google Scholar 

  2. Fuller-Pace FV (2013) The DEAD box proteins DDX5 (p68) and DDX17 (p72): multi-tasking transcriptional regulators. Biochim Biophys Acta 1829(8):756–763

    Google Scholar 

  3. Patil JR, Jayaprakasha GK, Chidambara Murthy KN, Tichy SE, Chetti MB, Patil BS (2009) Apoptosis-mediated proliferation inhibition of human colon cancer cells by volatile principles of Citrus aurantifolia. Food Chem 114:1351–1358

    Article  CAS  Google Scholar 

  4. Aggarwal BB, Kumar A, Bharti AC (2003) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23:363–398

    CAS  PubMed  Google Scholar 

  5. Du B, Jiang L, Xia Q, Zhong L (2006) Synergistic inhibitory effects of curcumin and 5-fluorouracil on the growth of the human colon cancer cell line HT-29. Chemotherapy 52:23–28

    Article  CAS  PubMed  Google Scholar 

  6. Lev-Ari S, Strier L, Kazanov D, Madar-Shapiro L, Dvory-Sobol H, Pinchuk I, Marian B, Lichtenberg D, Arber N (2005) Celecoxib and curcumin synergistically inhibit the growth of colorectal cancer cells. Clin Cancer Res 11:6738–6744

    Article  CAS  PubMed  Google Scholar 

  7. Lev-Ari S, Zinger H, Kazanov D, Yona D, Ben-Yosef R, Starr A, Figer A, Arber N (2005) Curcumin synergistically potentiates the growth inhibitory and proapoptotic effects of celecoxib in pancreatic adenocarcinoma cells. Biomed Pharmacother 59(Suppl. 2):S276–S280

    Article  CAS  PubMed  Google Scholar 

  8. Notarbartolo M, Poma P, Perri D, Dusonchet L, Cervello M, D’Alessandro N (2005) Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-jB activation levels and in IAP gene expression. Cancer Lett 224:53–65

    Article  CAS  PubMed  Google Scholar 

  9. Koo JY, Kim HJ, Jung KO, Park KY (2004) Curcumin inhibits the growth of AGS human gastric carcinoma cells in vitro and shows synergism with 5-fluorouracil. J Med Food 7:117–121

    Article  CAS  PubMed  Google Scholar 

  10. Chan MM, Fong D, Soprano KJ, Holmes WF, Heverling H (2003) Inhibition of growth and sensitization to cisplatinmediated killing of ovarian cancer cells by polyphenolic chemopreventive agents. J Cell Physiol 194:63–70

    Article  CAS  PubMed  Google Scholar 

  11. Hour TC, Chen J, Huang CY, Guan JY, Lu SH, Pu YS (2002) Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF-kappaB Activation. Prostate 51:211–218

    Article  CAS  PubMed  Google Scholar 

  12. Liu Y, Chang RL, Cui XX, Newmark HL, Conney AH (1997) Synergistic effects of curcumin on all-trans retinoic acid- and 1 alpha, 25-dihydroxyvitamin D3-induced differentiation in human promyelocytic leukemia HL-60 cells. Oncol Res 9:19–29

    CAS  PubMed  Google Scholar 

  13. Testa JR, Bellacosa A (2001) Akt plays a central role in tumorigenesis. Proc Natl Acad Sci USA 98:10983–10985

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Nicholson KM, Anderson NG (2002) The protein kinase B/Akt signaling pathway in human malignancy. Cell Signal 14:381–395

    Article  CAS  PubMed  Google Scholar 

  15. Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-kinase/AKT pathway in human cancer. Nat Rev Cancer 2:489–501

    Article  CAS  PubMed  Google Scholar 

  16. Datta SR, Brunet A, Greenberg ME (1999) Cellular survival: a play in three Akts. Genes Dev 13:2905–2927

    Article  CAS  PubMed  Google Scholar 

  17. Brazil DP, Yang Z, Hemmings BA (2004) Advances in protein kinase B signalling: AKTion on multiple fronts. Trends Biochem Sci 29:233–242

    Article  CAS  PubMed  Google Scholar 

  18. Al-Nasiry S, Geusens N, Hanssens M, Luyten C, Pijnenborg R (2007) The use of Alamar Blue assay for quantitative analysis of viability, migration and invasion of choriocarcinoma cells. Hum Reprod 22:1304–1309

    Article  CAS  PubMed  Google Scholar 

  19. Thomasset SC, Berry DP, Garcea G, Marczylo T, Steward WP, Gescher AJ (2007) Dietary polyphenolic phytochemicals—promising cancer chemopreventative agents in humans? A review of their clinical properties. Int J Cancer 120:451–458

    Article  CAS  PubMed  Google Scholar 

  20. Goel A, Kunnumakkara AB, Aggarwal BB (2008) Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol 75:787–809

    Article  CAS  PubMed  Google Scholar 

  21. Strimpakos AS, Sharma RA (2008) Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal 10:511–545

    Article  CAS  PubMed  Google Scholar 

  22. Testa JR, Bellacosa A (2001) Akt plays a central role in tumorigenesis. Proc Natl Acad Sci USA 98:10983–10985

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Nicholson KM, Anderson NG (2002) The protein kinase B/Akt signaling pathway in human malignancy. Cell Signal 14:381–395

    Article  CAS  PubMed  Google Scholar 

  24. Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-kinase/AKT pathway in human cancer. Nat Rev Cancer 2:489–501

    Article  CAS  PubMed  Google Scholar 

  25. Hofseth LJ, Hussain SP, Wogan GN, Harris CC (2003) Nitric oxide in cancer and chemoprevention. Free Radic Biol Med 4(8):955–968

    Article  Google Scholar 

  26. Zhang YH, Wei W, Xu H, Wang YY, Wu WX (2007) Inducing effects of hepatocyte growth factor on the expression of vascular endothelial growth factor in human colorectal carcinoma cells through MEK and PI3K signaling pathways. Chin Med J (Engl) 120(9):743–748

    CAS  Google Scholar 

  27. Vaux DL, Korsmeyer SJ (1999) Cell death in development. Cell 96:245–254

    Article  CAS  PubMed  Google Scholar 

  28. Srinivasula SM, Ahmad M, MacFarlane M, Luo Z, Huang Z, Fernandes-Alnemri T, Alnemri ES (1998) Generation of constitutively active recombinant caspases-3 and -6 by rearrangement of their subunits. J Biol Chem 273:10107–10111

    Article  CAS  PubMed  Google Scholar 

  29. Li X, Fan R, Zou X, Gao L, Jin H, Du R, Xia L, Fan D (2007) Inhibitory effect of recombinant adenovirus carrying immunocaspase-3 on hepatocellular carcinoma. Biochem Biophys Res Commun 358:489–494

    Article  CAS  PubMed  Google Scholar 

  30. Bao W, Zhang L, Jia L, Qu P, Wang C, Yang A (2004) Tumor suppression of a constitutively active caspase-3 in the SKBr-3 breast carcinoma xenograft mice model. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 20:23–26

    CAS  PubMed  Google Scholar 

  31. Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X (1997) Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275:1129–1132

    Article  CAS  PubMed  Google Scholar 

  32. Green DR (2005) Apoptotic pathways: ten minutes to dead. Cell 121:671–674

    Article  CAS  PubMed  Google Scholar 

  33. Twiddy D, Brown DG, Adrain C, Jukes R, Martin SJ, Cohen GM, MacFarlane M, Cain K (2004) Pro-apoptotic proteins released from the mitochondria regulate the protein composition and caspase-processing activity of the native Apaf-1/caspase-9 apoptosome complex. J Biol Chem 279:19665–19682

    Article  CAS  PubMed  Google Scholar 

  34. Martin MC, Allan LA, Lickrish M, Sampson C, Morrice N, Clarke PR (2005) Protein kinase A regulates caspase-9 activation by Apaf-1 downstream of cytochrome c. J Biol Chem 280:15449–15455

    Article  CAS  PubMed  Google Scholar 

  35. Yang J, Liu X, Bhalla K, Kim CM, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X (1997) Prevention of apoptosis by Bcl-2 release of cytochrome c from mitochondria blocked. Science 275:1129–1132

    Article  CAS  PubMed  Google Scholar 

  36. Solange D, Martinou JC (2000) Mitochondria as the central control point of apoptosis. Trends Cell Biol 10:369–377

    Article  Google Scholar 

  37. Sun J, Bi C, Chan HM, Sun S, Zhang Q, Zheng Y (2013) Curcumin-loaded solid lipid nanoparticles have prolonged in vitro antitumour activity, cellular uptake and improved in vivo bioavailability. Colloids Surf B Biointerfaces 111C:367–375

    Article  Google Scholar 

  38. Budihardjo I, Oliver H, Lutter M, Luo X, Wang X (1999) Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol 15:269–290

    Article  CAS  PubMed  Google Scholar 

  39. Salvesen G, Dixit V (1999) Caspase activation: the inducedproximity model. Proc Natl Acad Sci USA 96:10964–10967

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gastrointestinal Surgery Department, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, People’s Republic of China

    Qun Guang Jiang, Tai Yuan Li, Dong Ning Liu & Hai Tao Zhang

Authors
  1. Qun Guang Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tai Yuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dong Ning Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hai Tao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hai Tao Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jiang, Q.G., Li, T.Y., Liu, D.N. et al. PI3K/Akt pathway involving into apoptosis and invasion in human colon cancer cells LoVo. Mol Biol Rep 41, 3359–3367 (2014). https://doi.org/10.1007/s11033-014-3198-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3198-2

Keywords

Search

Navigation