Journal List > Korean J Urol > v.50(5) > 1005336

TOOLS
Lee, Park, Jang, Myung, and Kim: The Effects of Adiponectin and Leptin in the Proliferation of Prostate Cancer Cells
Original Article
Basic and Translational Research
Korean Journal of Urology

Korean Journal of Urology 2009; 50(5): 493-497.

Published online: 26 May 2009

DOI: https://doi.org/10.4111/kju.2009.50.5.493

The Effects of Adiponectin and Leptin in the Proliferation of Prostate Cancer Cells

Seo Yeon Lee, Se Jun Park, In Ho Jang, Soon Chul Myung, Tae Hyoung Kim

Department of Urology, College of Medicine, Chung-Ang University, Seoul, Korea.

Correspondence to: Tae Hyoung Kim. Department of Urology, College of Medicine, Chung-Ang University, 65-207, Hankang-ro 3-ga, Yongsan-gu, Seoul 140-757, Korea. TEL: 02-748-9978, FAX: 02-798-8577, kthlmk@hanafos.com

Received 24 December 2008       Accepted 20 April 2009

Copyright © The Korean Urological Association, 2009

Abstract

Purpose

With the westernization of dietary life, domestic prostate cancer prevalence has remarkably increased recently. Therefore, to examine the effects of obesity on prostate cancer, we analyzed the effects of leptin and adiponectin, which are the cytokines secreted from adipocytes, on prostate cancer in vitro and confirmed the results by in vivo experiment.

Materials and Methods

In vitro, the human androgen-independent prostate cancer cell line DU-145 was exposed to various concentrations of adiponectin and leptin, and their effects were measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vivo, the effects of tumor growth were observed in xenografted nude mice with prostate cancer.

Results

Adiponectin significantly repressed DU-145 cell growth in a dose-dependent manner. Leptin promoted DU-145 cell growth in dose-dependent manner, but it was not significant statistically. In vivo, adiponectin-treated mice demonstrated a reduced tumor volume, although it was not significant statistically. By contrast, leptin-treated mice showed a significantly increased tumor volume (p<0.01).

Conclusions

The in vitro and in vivo finding suggested that adiponectin suppresses the proliferation of prostate cancer cells and that leptin plays an important role in the proliferation of prostate cancer cells. We suggest that adiponectin and leptin have a relation to the progression of prostate cancer in the obese population.

Keywords: Prostatic neoplasms, Adiponectin, Leptin

Figures and Tables

Fig. 1
Survival rate of DU-145 cells according to adiponectin dose. a: p=0.005, b: p=0.023.
kju-50-493-g001
Fig. 2
Survival rate of DU-145 cells according to leptin dose. a: p>0.05.
kju-50-493-g002
Table 1
Correlation of the rate of tumor volume change and the number of injections
kju-50-493-i001

Notes

This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2007-331-E00153).

References

1. Song K, Song C, Ahn H. Continuing trends of the clinical parameter migration in patients with prostate cnacer in Korea. Korean J Urol. 2007. 48:574–578.
2. Bub JD, Miyazaki T, Iwamoto Y. Adiponectin as a growth inhibitor in prostate cancer cells. Biochem Biophys Res Commun. 2006. 340:1158–1166.
3. Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem. 2002. 277:25863–25866.
4. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002. 106:2767–2770.
5. Carroll KK. Obesity as a risk factor for certain types of cancer. Lipids. 1998. 33:1055–1059.
6. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004. 89:2548–2556.
7. Barb D, Williams CJ, Neuwirth AK, Mantzoros CS. Adioponectin in relation to malignancies: a review of existing basic research and clinical evidence. Am J Clin Nutr. 2007. 86:s858–s866.
8. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996. 334:292–295.
9. Chang S, Hursting SD, Contois JH, Strom SS, Yamamura Y, Babaian RJ, et al. Leptin and prostate cancer. Prostate. 2001. 46:62–67.
10. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999. 257:79–83.
11. Goktas S, Yilmaz MI, Caglar K, Sonmez A, Kilic S, Bedir S. Prostate cancer and adiponectin. Urology. 2005. 65:1168–1172.
12. Cao Y, O'Reilly MS, Marshall B, Flynn E, Ji RW, Folkman J. Expression of angiostatin cDNA in a murine fibrosarcoma suppresses primary tumor growth and produces long-term dormancy of metastases. J Clin Invest. 1998. 101:1055–1063.
13. Kissebah AH, Sonnenberg GE, Myklebust J, Goldstein M, Broman K, James RG, et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci USA. 2000. 97:14478–14483.
14. Takahashi M, Arita Y, Yamagata K, Matsukawa Y, Okutomi K, Horie M, et al. Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes Relat Metab Disord. 2000. 24:861–868.
15. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994. 372:425–432.
16. Nazian SJ, Cameron DF. Temporal relation between leptin and various indices of sexual maturation in the male rat. J Androl. 1999. 20:487–491.
17. Blum WF, Englaro P, Attanasio AM, Kiess W, Rascher W. Human and clinical perspectives on leptin. Proc Nutr Soc. 1998. 57:477–485.
18. Miyazaki T, Bub JD, Uzuki M, Iwamoto Y. Adiponectin activates c-Jun NH2-terminal kinase and inhibits signal transducer and activator of transcription 3. Biochem Biophys Res Commun. 2005. 333:79–87.
19. 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.
20. Cong L, Gasser J, Zhao J, Yang B, Li F, Zhao AZ. Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells, HEC-1-A and RL95 2. Endocr Relat Cancer. 2007. 14:713–720.
21. Yoneda K, Tomimoto A, Endo H, Iida H, Sugiyama M, Takahashi H, et al. Expression of adiponectin receptors, AdipoR1 and AdipoR2, in normal colon epithelium and colon cancer tissue. Oncol Rep. 2008. 20:479–483.
22. Wang XJ, Yuan SL, Lu Q, Lu YR, Zhang J, Liu Y, et al. Potential involvement of leptin in carcinogenesis of hepatocellular carcinoma. World J Gastroenterol. 2004. 10:2478–2481.
23. Onuma M, Bub JD, Rummel TL, Iwamoto Y. Prostate cancer cell-adipocyte interaction: leptin mediates androgen-independent prostate cancer cell proliferation through c-Jun NH2-terminal kinase. J Biol Chem. 2003. 278:42660–42667.
24. Somasundar P, Frankenberry KA, Skinner H, Vedula G, McFadden DW, Riggs D, et al. Prostate cancer cell proliferation is influenced by leptin. J Surg Res. 2004. 118:71–82.
25. Michalakis K, Williams CJ, Mitsiades N, Blakeman J, Balafouta-Tselenis S, Giannopoulos A, et al. Serum adiponectin concentrations and tissue expression of adiponectin receptors are reduced in patients with prostate cancer: a case control study. Cancer Epidemiol Biomarkers Prev. 2007. 16:308–313.
26. Baillargeon J, Platz EA, Rose DP, Pollock BH, Ankerst DP, Haffner S, et al. Obesity, adipokines, and prostate cancer in a prospective population-based study. Cancer Epidemiol Biomarkers Prev. 2006. 15:1331–1335.
27. Bub JD, Miyazaki T, Iwamoto Y. Adiponectin as a growth inhibitor in prostate cancer cells. Biochem Biophys Res Commun. 2006. 340:1158–1166.
28. Mistry T, Digby JE, Desai KM, Randeva HS. Leptin and adiponectin interact in the regulation of prostate cancer cell growth via modulation of p53 and bcl-2 expression. BJU Int. 2008. 101:1317–1322.
29. Ribeiro R, Lopes C, Medeiros R. The link between obesity and prostate cancer: the leptin pathway and therapeutic perspectives. Prostate Cancer Prostatic Dis. 2006. 9:19–24.
TOOLS
Similar articles