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Effect of lycopene on insulin-like growth factor-I, IGF binding protein-3 and IGF type-I receptor in prostate cancer cells

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Abstract

Purpose

Prostate cancer is the second most common cancer that leads to death in elderly men. The risk of prostate cancer prevalence is often associated with the elevated level of insulin-like growth factor-I (IGF-I) and decreased level of IGF-binding protein 3 (IGFBP-3). Lycopene, a carotenoid, reduces the proliferation of cancer cells and induces apoptosis. Hence, higher intake of lycopene can be associated with the lower risk of prostate cancer. However, the mechanism of action of lycopene in the prevention of prostate cancer is still unclear. The present study was carried out to study the effects of lycopene on the components of IGF system and apoptosis in androgen-independent prostate cancer cells (PC-3 cells).

Methods

PC-3 cells were treated with various concentrations of lycopene, (20, 40 and 60 μM) for 24, 48, 72 and 96 h. IGF-I, IGFBP-3 and IGF-I receptor (IGF-IR) levels in lycopene-treated cells were evaluated. Annexin V and propidium iodide (PI) binding studies were done to assess apoptosis.

Results

PC-3 cells treated with lycopene showed a significant decrease in cell proliferation. Lycopene, at a dose of 40 μM, significantly increased the level of IGFBP-3. Lycopene-induced apoptosis was confirmed by annexin V and PI binding. Lycopene-induced DNA fragmentation was absent after 24 h treatment whereas the same was observed after 48 h treatment. There was a significant decrease in the IGF-IR expression after the cells were treated with lycopene and IGF-I.

Conclusion

The data obtained suggest that the components of the IGF system may act as a positive regulator of lycopene-induced apoptosis in PC-3 cells. Thus, the observed lycopene-induced biological effects and their associated mechanisms are encouraging and may lead to the development of a highly successful drug for the treatment of prostate cancer.

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References

  • Angelloz-Nicoud P, Binoux M (1995) Autocrine regulation of cell proliferation by the insulin-like growth factor (IGF) and IGF binding protein-3 protease system in a human prostate carcinoma cell line (PC-3). Endocrinology 136:5485–5492

    Article  PubMed  CAS  Google Scholar 

  • Chan M, Stampfer J, Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M (1998) Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279:563–566

    Article  PubMed  CAS  Google Scholar 

  • Chaudhary KS, Abel PD, Stamp GWH, Lalani E (2001) Differential expression of cell death regulators in response to thapsigargin and adriamycin in Bcl-2 transfected DU145 prostatic cancer cells. J Pathol 193:522–529

    Article  PubMed  CAS  Google Scholar 

  • Gerster H (1997) The potential role of lycopene for human health. J Am Coll Nutr 16:109–126

    PubMed  CAS  Google Scholar 

  • Giovannucci E (2002) A review of epidemiologic studies of tomatoes, lycopene, and prostate cancer. Exp Biol Med 227:852–859

    CAS  Google Scholar 

  • Hall AK (1996) Liarozole amplifies retinoid-induced apoptosis in human prostate cells. Anticancer Drugs 7:312–320

    Article  PubMed  CAS  Google Scholar 

  • Hantz HL, Young LF, Martin KR (2005) Physiologically attainable concentration of lycopene induced mitochondrial apoptosis in LNCaP human prostate cancer cells. Exp Biol Med 2030:171–179

    Google Scholar 

  • Huynh H, Yang X, Pollak M (1996) Estradiol and anti-estrogens regulate a growth inhibitory insulin-like growth factor binding protein-3 autocrine loop in human breast cancer cells. J Biol Chem 271:1061–1021

    Article  Google Scholar 

  • Huynh H, Pollak M, Zhang JC (1998) Regulation of insulin-like growth factor (IGF) II and IGF binding protein 3 autocrine loop in human PC-3 prostate cancer cells by vitamin D metabolite 1,25(OH)2D3 and its analog EB1089. Int J Oncol 13:137–143

    PubMed  CAS  Google Scholar 

  • Hwang ES, Bowen PE (2005) Effects of tomato paste extracts on cell proliferation, cell-cycle arrest and apoptosis in LNCaP human prostate cancer cells. Biofactors 23:75–84

    PubMed  CAS  Google Scholar 

  • Iwamura M, Sluss PM, Casamento JB, Cockett AT (1993) Insulin-like growth factor-I: action and receptor characterization in human prostate cell lines. Prostate 22:243–252

    Article  PubMed  CAS  Google Scholar 

  • Kaicer E, Blat C, Harel L (1991) IGF-I and IGF binding proteins: stimulatory and inhibitory factors secreted by human prostatic adenocarcinoma cells. Growth Factors 4:231–237

    PubMed  CAS  Google Scholar 

  • Kaighn ME, Narayan KS, Ohnuki Y, Lechner JF, Jones LW (1979) Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urol 17:16–23

    PubMed  CAS  Google Scholar 

  • Karas M, Amir H, Fishman D, Danilenko M, Segal S, Nahum A, Koifmann A, Giat Y, Levy J, Sharoni Y (2000) Lycopene interfere with cell cycle progression and insulin-like growth factor-I signaling in mammary cancer. Nutr Cancer 36:101–111

    Article  PubMed  CAS  Google Scholar 

  • Kelin RD, Fischer SM (2002) Black tea polyphenols inhits IGF-I induced signal pathway through Akt in normal prostate epithelial cells and DU 145 prostate carcinoma cells. Carcinogenesis 23:217–221

    Article  Google Scholar 

  • Kim L, Rao AV, Rao LG (2002) Effect of lycopene on prostate LNCaP cancer cells in culture. J Med Food 5:181–187

    Article  PubMed  CAS  Google Scholar 

  • Kimura G, Kasuva J, Giannini S, Honda Y, Mohan S, Kawachi M, Akimoto M, Fujita-Yamaguchi Y (1996) Insulin-like growth factor (IGF) system components in human prostatic cancer cell-lines: LNCaP, DU145, and PC-3 cells. Int J Urol 3:39–46

    PubMed  CAS  Google Scholar 

  • Koopman G, Reutelingsperger CP, Kuijten GA, Keehnen RM, Pals ST, van Oers MH (1994) Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood 84:1415–1420

    PubMed  CAS  Google Scholar 

  • Kotake-Nara E, Kushiro M, Zhang H, Sugawara T, Miyashita K, Nagao A (2001) Carotenoids affect proliferation of human prostate cells. J Nutr 131:3303–3306

    PubMed  CAS  Google Scholar 

  • Kotake-Nara E, Kim SJ, Kobori M, Miyashita K, Nagao A (2002) Acyclo-retinoic acid induces apoptosis in human prostate cancer cells. Anticancer Res 22:689–695

    PubMed  CAS  Google Scholar 

  • Liu C, Lian F, Smith DE, Russell RM, Wang XD (2003) Lycopene supplementation inhibits lung squamous metaplasia and induces apoptosis via up-regulating insulin-like growth factor-binding protein 3 in cigarette smoke-exposed Ferrets. Cancer Res 63:3138–3144

    PubMed  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  • Miles LEM, Lipschitz DA, Bieber CP, Cook JD (1974) Measurement of serum ferritin by a 2-site immunoradiometric assay. Anal Biochem 61:209–224

    Article  PubMed  CAS  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 16:55–63

    Article  Google Scholar 

  • Newling DW (1996a) Anti-androgens in the treatment of prostate cancer. Br J Urol 7:776–784

    Google Scholar 

  • Newling DW (1996b) The management of hormone refractory prostate cancer. Eur Urol 29:69–74

    Google Scholar 

  • Park YO, Hwang ES, Moon TW (2005) The effect of lycopene on cell growth and oxidative DNA damage of Hep3B human hepatoma cells. Biofactors 23:129–139

    PubMed  CAS  Google Scholar 

  • Pastori M, Pfander H, Boscoboinik D, Azzi A (1998) Lycopene in association with alpha-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells. Biochem Biophys Res Commun 250:582–585

    Article  PubMed  CAS  Google Scholar 

  • Pietrzkowski Z, Mulholland G, Goomella L, Jameson BA, Wernicke D, Baserga B (1993) Inhibition of growth of prostate cancer cell lines by peptide analogue of insulin-like growth factor I. Cancer Res 53:1102–1106

    PubMed  CAS  Google Scholar 

  • Rajah R, Valentinis B, Cohen P (1997) Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-β1 on programmed cell death through a p53 and IGF-independent mechanism. J Biol Chem 272:12181–12188

    Article  PubMed  CAS  Google Scholar 

  • Rajah R, Khare A, Lee PD, Cohen P (1999) Insulin-like growth factor-binding protein-3 is partially responsible for high-serum-induced apoptosis in PC-3 prostate cancer cells. J Endocrinol 163:487–494

    Article  PubMed  CAS  Google Scholar 

  • Scher HI, Steineck G, Kelly WK (1995) Hormone refractory (D3) prostate cancer: refining the concept. Urology 46:142–148

    Article  PubMed  CAS  Google Scholar 

  • Tang L, Jin T, Zeng X, Wang JS (2005) Lycopene inhibits the growth of human androgen-independent prostate cancer cells in vitro and in BALB/c nude mice. J Nutr 135:287–290

    PubMed  CAS  Google Scholar 

  • Vainas IG (2001) Octreotide in the management of hormone-refractory prostate cancer. Chemotherapy 47:109–129

    Article  PubMed  CAS  Google Scholar 

  • Vijayababu MR, Kanagaraj P, Arunkumar A, Ilangovan R, Aruldhas MM, Arunakaran J (2005) Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression. J Cancer Res Clin Oncol 131:765–771

    Article  PubMed  CAS  Google Scholar 

  • Vijayababu MR, Kanagaraj P, Arunkumar A, Ilanagovan R, Dharmarajan A, Arunakaran J (2006) Quercetin induces p53-independent apoptosis in human prostate cancer cells by modulating Bcl-2 related proteins: a possible mediation by IGFBP-3. Oncol Res 16:67–74

    PubMed  CAS  Google Scholar 

  • Wetterau LA, Francis MJ, Ma L, Cohen P (2003) Insulin-like growth factor I stimulates telomerase activity in prostate cancer cells. J Clin Endocrinol Metab 88:3354–3359

    Article  PubMed  CAS  Google Scholar 

  • Wolk A, Mantzoros CS, Andersson SO, Bergstrom R, Signorello LB, Lagiou P, Adami HO, Trichopoulos D (1998) Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study. J Natl Cancer Inst 17:911–915

    Article  Google Scholar 

  • Zhang J, Jung K, Lein M, Kristiansen G, Rudolph B, Hauptmann S, Schnorr D, Loening SA, Lichtinghagen R (2002) Differential expression of matrix metalloproteinases and their tissue inhibitors. Prostate 50:38–45

    Article  PubMed  CAS  Google Scholar 

  • Zi X, Zhang J, Agarwal R, Pollak M (2000) Silibinin up-regulates insulin-like growth factor-binding protein-3 expression and inhibits proliferation of androgen-independent prostate cancer cells. Cancer Res 60:5617–5620

    PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank Dr. P. Mullainathan (Department of Zoology, University of Madras, Chennai, India) for his kind help and valuable suggestions towards this study. Financial assistance from Council of Scientific and Industrial Research (CSIR) in the form of SRF (Grant no. 9/615 (622)/2004-EMR-I dt. 30-06-2004) is gratefully acknowledged. The authors gratefully acknowledge the effort of the copy editor Mr. M. Vijayaraman in improving the language of our manuscript.

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Authors and Affiliations

  1. Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, India

    P. Kanagaraj, M. R. Vijayababu, B. Ravisankar, J. Anbalagan, M. M. Aruldhas & J. Arunakaran

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  1. P. Kanagaraj
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  2. M. R. Vijayababu
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  3. B. Ravisankar
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  4. J. Anbalagan
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  5. M. M. Aruldhas
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  6. J. Arunakaran
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Correspondence to J. Arunakaran.

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Kanagaraj, P., Vijayababu, M.R., Ravisankar, B. et al. Effect of lycopene on insulin-like growth factor-I, IGF binding protein-3 and IGF type-I receptor in prostate cancer cells. J Cancer Res Clin Oncol 133, 351–359 (2007). https://doi.org/10.1007/s00432-006-0177-6

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  • DOI: https://doi.org/10.1007/s00432-006-0177-6

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