Molecular and Cellular Biochemistry

, Volume 448, Issue 1–2, pp 125–135 | Cite as

Adiponectin and colon cancer: evidence for inhibitory effects on viability and migration of human colorectal cell lines

  • E. Nigro
  • P. Schettino
  • R. Polito
  • O. Scudiero
  • M. L. Monaco
  • G. D. De Palma
  • A. Daniele


Adiponectin (Acrp30) is an adipokine widely studied for its beneficial metabolic and anti-inflammatory properties. Colorectal cancer is among the most common cancers worldwide. The aim of present study was to explore the effects of Acrp30 on both CaCo-2 and HCT116 colorectal cancer cells in terms of viability, oxidative stress, and apoptosis. In addition, since colorectal cancer represents a typical inflammation-related cancer, we investigated whether Acrp30 treatment modifies the migration and the expression of crucial proteins in the EMT transition. Finally, we analyzed the expression of cytokines in CaCo-2 cells. We found that Acrp30 reduces the survival rate of both CaCo-2 and HCT116 cells through induction of apoptosis and oxidative stress already after 24 h of treatment. In addition, wound-healing assay indicated that Acrp30 exposure statistically inhibits CaCo-2 and HCT116 cell migration. Western blot analysis performed on E-cadherin and vimentin, two EMT crucial markers in carcinogenesis, indicated that Acrp30 does not influence EMT transition. Finally, we found a reduction of mRNA levels corresponding to the anti-inflammatory IL-10 cytokine together with an increase of the pro-inflammatory IL-6 and IL-8 cytokines. This study provides new insight into Acrp30 molecular effects on colorectal cancer cells. Indeed, even if further studies are necessary to clarify the precise role of Acrp30 in colorectal cancer, our data strongly suggest that Acrp30 negatively regulates cell survival and migration in association with induction of oxidative stress and regulation of cytokines expression in both CaCo-2 and HCT116 colorectal cells.


Adiponectin Colorectal cancer Cell proliferation and apoptosis Migration Cytokines 



We acknowledge “Fondazione La casa della Speranza Onlus” via Alois 81100, Caserta, Italy.

Author contributions

AD and EN convinced the study. PS and EN performed the experiments together with RP and MLM. OS performed the statistical analysis. AD and GDDP wrote the manuscript with the help of PS and EN. AD did the final revision of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Coelho M, Oliveira T, Fernandes R (2013) Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci 9:91–200Google Scholar
  2. 2.
    Nigro E, Scudiero O, Monaco ML et al (2014) New insight into adiponectin role in obesity and obesity-related diseases. Biomed Res Int 2014:14CrossRefGoogle Scholar
  3. 3.
    Lee B, Shao J (2014) Adiponectin and energy homeostasis. Rev Endocr Metabol Disord 15:149–156CrossRefGoogle Scholar
  4. 4.
    Mather JK (2014) Clinical use of adiponectin as a marker of metabolic dysregulation. Best Pract Res Clin Endocrinol Metab 1:107–117CrossRefGoogle Scholar
  5. 5.
    Ackerman SE, Blackburn OA, Marchildon F, Cohen P (2017) Insights into the link between obesity and cancer. Curr Obes Rep 6:195–203CrossRefGoogle Scholar
  6. 6.
    Robinson K, Prins J, Venkatesh B (2011) Clinical review: adiponectin biology and its role in inflammation and critical illness. Crit Care 15:221CrossRefGoogle Scholar
  7. 7.
    Liu M, Liu F (2014) Regulation of adiponectin multimerization, signaling and function. Best Pract Res Clin Endocrinol Metab 28:25–31CrossRefGoogle Scholar
  8. 8.
    Denzel MS, Scimia MC, Zumstein PM et al (2010) T-cadherin is critical for adiponectin-mediated cardioprotection in mice. J Clin Invest 120:4342–4352CrossRefGoogle Scholar
  9. 9.
    Ouchi N, Parker JL, Lugus JJ et al (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11:85–97CrossRefGoogle Scholar
  10. 10.
    Dalamaga M, Christodoulatos GS (2015) Adiponectin as a biomarker linking obesity and adiposopathy to hematologic malignancies. Horm Mol Biol Clin Investig 23:5–20PubMedGoogle Scholar
  11. 11.
    Wei T, Ye P, Peng X et al (2016) Circulating adiponectin levels in various malignancies: an updated meta-analysis of 107 studies. Oncotarget 7:48671–48691PubMedPubMedCentralGoogle Scholar
  12. 12.
    Hossain MM, Mukheem A, Kamarul T (2015) The prevention and treatment of hypoadiponectinemia-associated human diseases by up-regulation of plasma adiponectin. Life Sci 135:55–67CrossRefGoogle Scholar
  13. 13.
    Joshi RK, Kim WJ, Lee SA (2014) Association between obesity-related adipokines and colorectal cancer: a case-control study and meta-analysis. World J Gastroenterol 20:7941–7949CrossRefGoogle Scholar
  14. 14.
    Bråkenhielm E, Veitonmäki N, Cao R et al (2004) Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci USA 101:2476–2481CrossRefGoogle Scholar
  15. 15.
    Daniele A, De Rosa A, Nigro E et al (2012) Adiponectin oligomerization state and adiponectin receptors airway expression in chronic obstructive pulmonary disease. Int J Biochem Cell Biol 44:563–569CrossRefGoogle Scholar
  16. 16.
    Dalamaga M, Diakopoulos KN, Mantzoros CS (2012) The role of adiponectin in cancer: a review of current evidence. Endocr Rev 33:547–594CrossRefGoogle Scholar
  17. 17.
    Kim AY, Lee YS, Kim KH et al (2010) Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation. Mol Endocrinol 24:1441–1452CrossRefGoogle Scholar
  18. 18.
    Okazaki M, Fushida S, Harada S et al (2010) Establishing a xenograft mouse model of peritoneal dissemination of gastric cancer with organ invasion and fibrosis. Cell Tissue Res 342:39–51CrossRefGoogle Scholar
  19. 19.
    Wang H, Wang H, Zhou B et al (2013) Epithelial–mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer. PLoS ONE 8(2):e56664CrossRefGoogle Scholar
  20. 20.
    Hyun Tae C, Kim S, Jung S et al (2014) Involvement of adiponectin in early stage of colorectal carcinogenesis. BMC Cancer 14:811CrossRefGoogle Scholar
  21. 21.
    Wright M, Beaty JS, Ternent CA (2017) Molecular markers for colorectal cancer. Surg Clin North Am 97:683–701CrossRefGoogle Scholar
  22. 22.
    Pecoraro A, Nigro E, Polito R et al (2017) Total and high molecular weight adiponectin expression is decreased in patients with common variable immunodeficiency: correlation with ig replacement therapy. Front Immunol 8:895CrossRefGoogle Scholar
  23. 23.
    Arnav K, Tan H (2016) Evolving role of adiponectin in cancer-controversies and update. Cancer Biol Med 13:101–119CrossRefGoogle Scholar
  24. 24.
    Sugiyama M, Takahashi H, Hosono K et al (2009) Adiponectin inhibits colorectal cancer cell growth through the AMPK/mTOR pathway. Int J Oncol 34:339–344PubMedGoogle Scholar
  25. 25.
    Ogunwobi OO, Beales IL (2006) Adiponectin stimulates proliferation and cytokine secretion in colonic epithelial cells. Regul Pept 134:105–113CrossRefGoogle Scholar
  26. 26.
    Matsuda M, Shimomura I (2014) Roles of Acrp30 and oxidative stress in obesity-associated metabolic and cardiovascular diseases. Rev Endocr Metab Disord 15:1–10CrossRefGoogle Scholar
  27. 27.
    Illiano M, Sapio L, Caiafa I, Spina A, Scudiero O. Bianco A, Esposito S, Mazzeo F, Pedone PV (2017) Adiponectin down-regulates CREB and inhibits proliferation of A549 lung cancer cells. Pulm Pharmacol 45:114–120CrossRefGoogle Scholar
  28. 28.
    Wang Y, Lam KS, Xu JY et al (2005) Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem 280:18341–18347CrossRefGoogle Scholar
  29. 29.
    Wang Y, Lam KS, Yau MH, Xu A (2008) Post-translational modifications of adiponectin: mechanisms and functional implications. Biochem J 409:23–633CrossRefGoogle Scholar
  30. 30.
    Subedi A, Kim MJ, Nepal S et al (2013) Globular adiponectin modulates expression of programmed cell death 4 and miR-21 in RAW 264.7 macrophages through the MAPK/NF-κB pathway. FEBS Lett 587:1556–1561CrossRefGoogle Scholar
  31. 31.
    Nigro E, Scudiero O, Sarnataro D et al (2013) Adiponectin affects lung epithelial A549 cell viability counteracting TNFα and IL-1ß toxicity through AdipoR1. Int J Biochem Cell Biol 45:1145–1153CrossRefGoogle Scholar
  32. 32.
    Miyazaki T, Bub JD, Uzuki M et al (2005) Adiponectin activates c-Jun NH2-terminal kinase and inhibits signal transducer and activator of transcription 3. Biochem Biophys Res Commun 333:79–87CrossRefGoogle Scholar
  33. 33.
    Taliaferro-Smith L, Nagalingam A, Zhong D et al (2009) LKB1 is required for adiponectin-mediated modulation of AMPK–S6K axis and inhibition of migration and invasion of breast cancer cells. Oncogene 28:2621–2633CrossRefGoogle Scholar
  34. 34.
    Moon HS, Liu X, Nagel JM et al (2013) Salutary effects of adiponectin on colon cancer: in vivo and in vitro studies in mice. Gut 62:561–570CrossRefGoogle Scholar
  35. 35.
    Fan D, Li L, Wang C et al (2011) Adiponectin induces interleukin-6 production and its underlying mechanism in adult rat cardiac fibroblasts. J Cell Physiol 226:1793–1802CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • E. Nigro
    • 1
    • 2
  • P. Schettino
    • 3
  • R. Polito
    • 1
    • 4
  • O. Scudiero
    • 1
    • 5
  • M. L. Monaco
    • 1
  • G. D. De Palma
    • 3
  • A. Daniele
    • 1
    • 4
  1. 1.CEINGE-Biotecnologie Avanzate ScarlNapoliItaly
  2. 2.Dipartimento di Medicina e Scienze della SaluteUniversità del MoliseCampobassoItaly
  3. 3.Dipartimento di Medicina Clinica e ChirurgiaUniversità di Napoli Federico IINapoliItaly
  4. 4.Dipartimento di Scienze e Tecnologie Ambientali Biologiche FarmaceuticheUniversità degli Studi della Campania, “Luigi Vanvitelli”CasertaItaly
  5. 5.Dipartimento di Medicina Molecolare e Biotecnologie MedicheUniversità di Napoli Federico IINapoliItaly

Personalised recommendations