Horm Metab Res 2007; 39(1): 9-13
DOI: 10.1055/s-2007-956518
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Antiproliferative Effect of Adiponectin on MCF7 Breast Cancer Cells: A Potential Hormonal Link between Obesity and Cancer

J. D. Arditi 1 , M. Venihaki 1 , 2 , K. P. Karalis 1 , G. P. Chrousos 1 , 3
  • 1Departments of Endocrinology and Metabolism and Developmental Biology, Foundation of Biomedical Research of the Academy of Athens, Athens, Greece
  • 2Current address: Department of Clinical Chemistry-Biochemistry, School of Medicine, University of Crete, Crete, Greece
  • 3First Department of Pediatrics, Athens University Medical School, Athens, Greece
Weitere Informationen

Publikationsverlauf

Received 27. 4. 2006

Accepted 17. 10. 2006

Publikationsdatum:
16. Januar 2007 (online)

Abstract

Adiponectin, a hormone secreted by adipose tissue, circulates at high concentrations in human plasma. Paradoxically, plasma levels of adiponectin are approximately 50% lower in obese than in lean subjects. An association between low plasma levels of adiponectin and higher risk of developing breast and other cancers was recently reported. Obesity and overweight have also been associated with increased mortality from cancer. To test the hypothesis that adiponectin exerts direct antiproliferative and/or pro-apoptotic effects on cancer cells, we used the MCF7 human breast adenocarcinoma cell line. The proliferation rate of the MCF7 cells was measured using the MTT method, while apoptosis was examined by quantifying the DNA fragmentation using an ELISA assay. In addition, adiponectin receptor 1 (AdipoR1) and AdipoR2 mRNA expression was detected using RT-PCR. Adiponectin diminished the proliferation rate of MCF7 cells; this effect was significant after 48-96 hours of treatment. The presence of receptor expression suggested that the effect of adiponectin on cell proliferation was most likely specific and adiponectin receptor-mediated. Adiponectin induced no apoptosis of MCF7 cells over 48 hours. We conclude that adiponectin inhibits proliferation but causes no apoptosis of MCF7 breast cancer cells. These data suggest that adiponectin may represent a direct hormonal link between obesity and cancer.

References

  • 1 Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults.  N Engl J Med. 2003;  348 1625-1638
  • 2 Heliovaara MK, Strandberg TE, Karonen SL, Ebeling P. Association of serum adiponectin concentration to lipid and glucose metabolism in healthy humans.  Horm Metab Res. 2006;  38 336-340
  • 3 Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.  Biochem Biophys Res Commun. 1999;  257 79-83
  • 4 Miyoshi Y, Funahashi T, Kihara S, Taguchi T, Tamaki Y, Matsuzawa Y, Noguchi S. Association of serum adiponectin levels with breast cancer risk.  Clin Cancer Res. 2003;  9 5699-5704
  • 5 Mantzoros C, Petridou E, Dessypris N, Chavelas C, Dalamaga M, Alexe DM, Papadiamantis Y, Markopoulos C, Spanos E, Chrousos G, Trichopoulos D. Adiponectin and breast cancer risk.  J Clin Endocrinol Metab. 2004;  89 1102-1107
  • 6 Chen DC, Chung YF, Yeh YT, Chaung HC, Kuo FC, Fu OY, Chen HY, Hou MF, Yuan SS. Serum adiponectin and leptin levels in Taiwanese breast cancer patients.  Cancer Lett. 2006;  237 109-114
  • 7 Petridou E, Mantzoros C, Dessypris N, Koukoulomatis P, Addy C, Voulgaris Z, Chrousos G, Trichopoulos D. Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece.  J Clin Endocrinol Metab. 2003;  88 993-997
  • 8 Dal Maso L, Augustin LS, Karalis A, Talamini R, Franceschi S, Trichopoulos D, Mantzoros CS, La Vecchia C. Circulating adiponectin and endometrial cancer risk.  J Clin Endocrinol Metab. 2004;  89 1160-1163
  • 9 Ishikawa M, Kitayama J, Kazama S, Hiramatsu T, Hatano K, Nagawa H. Plasma adiponectin and gastric cancer.  Clin Cancer Res. 2005;  11 466-472
  • 10 Wei EK, Giovannucci E, Fuchs CS, Willett WC, Mantzoros CS. Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study.  J Natl Cancer Inst. 2005;  97 1688-1694
  • 11 Chinetti G, Zawadski C, Fruchart JC, Staels B. Expression of adiponectin receptors in human macrophages and regulation by agonists of the nuclear receptors PPARalpha, PPARgamma, and LXR.  Biochem Biophys Res Commun. 2004;  314 151-158
  • 12 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
  • 13 Burow ME, Tang Y, Collins-Burow BM, Krajewski S, Reed JC, McLachlan JA, Beckman BS. Effects of environmental estrogens on tumor necrosis factor alpha-mediated apoptosis in MCF-7 cells.  Carcinogenesis. 1999;  20 2057-2061
  • 14 Gustafson B, Jack MM, Cushman SW, Smith U. Adiponectin gene activation by thiazolidinediones requires PPAR gamma 2, but not C/EBP alpha-evidence for differential regulation of the aP2 and adiponectin genes.  Biochem Biophys Res Commun. 2003;  308 933-939
  • 15 Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients.  Arterioscler Thromb Vasc Biol. 2000;  20 1595-1599
  • 16 Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G. Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression.  Diabetes. 2003;  52 1779-1785
  • 17 Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, Arita Y, Okamoto Y, Shimomura I, Hiraoka H, Nakamura T, Funahashi T, Matsuzawa Y. Association of hypoadiponectinemia with coronary artery disease in men.  Arterioscler Thromb Vasc Biol. 2003;  23 85-89
  • 18 Adamczak M, Wiecek A, Funahashi T, Chudek J, Kokot F, Matsuzawa Y. Decreased plasma adiponectin concentration in patients with essential hypertension.  Am J Hypertens. 2003;  16 72-75
  • 19 Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects.  nature. 2003;  423 762-769
  • 20 Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages.  Blood. 2000;  96 1723-1732
  • 21 Brakenhielm E, Veitonmaki N, Cao R, Kihara S, Matsuzawa Y, Zhivotovsky B, Funahashi T, Cao Y. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis.  Proc Natl Acad Sci USA. 2004;  101 2476-2481
  • 22 Kang JH, Lee YY, Yu BY, Yang BS, Cho KH, Yoon DK, Roh YK. Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell.  Arch Pharm Res. 2005;  28 1263-1269
  • 23 Dieudonne MN, Bussiere M, Dos Santos E, Leneveu MC, Giudicelli Y, Pecquery R. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells.  Biochem Biophys Res Commun. 2006;  345 271-279

Correspondence

J. D. Arditi

Departments of Endocrinology and Metabolism and Developmental Biology

Foundation of Biomedical Research of the Academy of Athens

Soranou Ephessiou 4

115-27 Athens

Greece

Telefon: +30210659 70 00

Fax: +30210659 75 45

eMail: jarditi@bioacademy.gr