Skip to main content

Advertisement

SpringerLink
Log in

Regulation of the extracellular matrix remodeling by lutein in dermal fibroblasts, melanoma cells, and ultraviolet radiation exposed fibroblasts

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

With aging and cancer there is increased expression or activity of matrix metalloproteinases (MMPs) that degrade and remodel the structural extracellular matrix (ECM). In addition, exposure of skin to ultraviolet (UV) radiation (photoaging) leads to loss of cell viability, membrane damage, and deposition of excessive elastotic material. Lutein has antioxidant, anti-inflammatory, photoprotective, and anti-carcinogenic properties. The goal of this research was to investigate lutein’s anti-aging and anti-carcinogenic effects via the regulation of the extracellular matrix remodeling. To this purpose, the effects of lutein on the expression of MMPs and their inhibitors (TIMPs, tissue inhibitors of metalloproteinases) in dermal fibroblasts (intrinsic aging) and melanoma cells were examined. Further, for lutein’s photoprotective effects, the regulation of cell viability, membrane integrity, and elastin expression in the non-irradiated, and UVA or UVB radiation exposed fibroblasts were analyzed. Lutein significantly inhibited MMP-1 expression, transcriptionally, and MMP-2 protein levels in dermal fibroblasts, without altering TIMPs expression. It significantly inhibited MMP-1 expression in melanoma cells while stimulating TIMP-2. Lutein did not alter fibroblast or melanoma cell viability or membrane integrity. In ultraviolet radiation exposed fibroblasts, lutein improved cell viability, membrane integrity and inhibited elastin expression, though more significantly in the UVB exposed fibroblasts. In summary, the mechanism to lutein’s anti-aging and anti-carcinogenic effects include the inhibition of MMP to TIMP ratio in dermal fibroblasts and melanoma cells, and the inhibition of cell loss, membrane damage and elastin expression in ultraviolet radiation exposed fibroblasts.

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

Similar content being viewed by others

References

  • Astner S, Wu A, Chen J, Philips N, Rius-Diaz F, Parrado C, Mihm MC, Goukassian DA, Pathak MA, and González, S (2007) Dietary lutein/zeaxanthin reduces photoaging and photocarcinogenesis in chronically UVB irradiated SKH-1 hairless mice. Skin Pharmacol Physiol (in press)

  • Beatty S, Boulton M, Henson D, Koh HH, Murray IJ (1999) Macular pigment and age related macular degeneration. Br J Ophthalmol 83:867–877

    Article  PubMed  CAS  Google Scholar 

  • Bernd A, Ramirez-Bosca A, Huber H, Diaz-Alperi J, Thaci D, Sewell A Auintanilla-Almagro E, Holzmann H (1995). In vitro studies on the immunomodulating effects of poloypodium leucotomos extract on human leukocyte fractions. Arzneim-Forsch Drug Res 45:901–904

    CAS  Google Scholar 

  • Broekmans WMR, Berendschot TTJM, Klöpping-Ketelaars IAA, de Vries AJ, Goldbohm RA, Tjiburg BM (2002) Macular pigment density in relation to serum and adipose tissue concentrations of lutein and serum concentrations of zeaxanthin. Am J Clin Nutr 76:595–603

    PubMed  CAS  Google Scholar 

  • Clark LC, Combs GF, Turnbull BW, Slate EH, Chalker DK, Chow J et al (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA 276:1957–1963

    Article  PubMed  CAS  Google Scholar 

  • Dalle Carbonare M, Pathak MA (1992) Skin photosensitizing agents and the role of reactive oxygen species in photoaging. J Photochem Photobiol B 14:105–124

    Article  PubMed  CAS  Google Scholar 

  • Damiani E, Rosati L, Castagna R, Carloni P, Greci L (2006) Changes in ultraviolet absorbance and hence in protective efficacy against lipid peroxidation of organic sunscreens after UVA irradiation. J Photochem Photobiol B 82:204–213

    Article  PubMed  CAS  Google Scholar 

  • Darr D, Pinnell SR (1997) Reactive oxygen species and antioxidants protection in photodermatology. Sunscreens. Lowe NJ, Shaat NA, Pathak MA (eds) Marcel Dekker, New York, pp 155–173

  • Dickson RB, Lippman ME (1995). Growth factors in breast cancer. Endocr Rev 16:559–589

    Article  PubMed  CAS  Google Scholar 

  • Djavaheri-Mergny M, Mergny JL, Bertrand F, Santus R, Maziere C, Dubertret L, Maziere JC (1996). Ultraviolet-A induces activation of AP-1 in cultured human keratinocytes. FEBS Lett 384:92–96

    Article  PubMed  CAS  Google Scholar 

  • Dwyer JH, Mohamed N, Dwyer KM, Kholood H, Sun P, Shircore A, Hama- Levy S (2001) Oxygenated carotenoid lutein and progression of early atherosclerosis. The Los Angeles atherosclerosis study. Circulation 103:2922–2927

    PubMed  CAS  Google Scholar 

  • Fitzpatrick TB (1988) The validity and practicality of sun reactive skin type I-VI. Arch Dermatol 124:869–871

    Article  PubMed  CAS  Google Scholar 

  • Giacomoni PU, Rein G (2001) Factors of skin ageing share common mechanisms. Biogerontology 2:219–229

    Article  PubMed  CAS  Google Scholar 

  • González S, Moran M, Kochevar IE (1999) Chronic photodamage in skin of mast cell-deficient mice. Photochem Photobiol 70:248–253

    Article  PubMed  Google Scholar 

  • González S, Pathak MA (1996) Inhibition of ultraviolet-induced formation of reactive oxygen species, lipid peroxidation, erythema, and skin photosensitization by Polypodium leucotomos. Photodermatol Photoimmunol Photomed 12:45–56

    PubMed  Google Scholar 

  • Gonzalez S, Astner S, An W, Goukassian D, Pathak MA (2003) Dietary lutein/zeaxanthin decreases ultraviolet B-induced epidermal hyperproliferation and acute inflammation in hairless mice. J Invest Dermatol 121:399–405

    Article  PubMed  CAS  Google Scholar 

  • Ingram D (1994) Diet and subsequent survival in women with breast cancer. Br J Cancer 69:71–80

    Google Scholar 

  • Jain M, Miller AB, To T (1994) Premorbid diet and the prognosis of women with breast cancer. J Natl Cancer Inst 86:1390–1397

    Article  PubMed  CAS  Google Scholar 

  • Janczyk A, Garcia-Lopez MA, Penas P, Alonso-Lebrero JL, Benedicto I, Lopez-Cabrera, Gonzalez S (2007) A Polypodium leucotomos extract (PL) inhibits solar-simulated radiation-induced TNF-a and iNOS expression, transcriptional activation and apoptosis. Exp Dermatol (in press)

  • Kao RT, Stern R (1986). Collagenases in human breast carcinoma cell lines. Cancer Res 46:1349–1354

    PubMed  CAS  Google Scholar 

  • Khachik F, Beecher GR, Smith JC (1995) Lutein, lycopene, and their oxidative metabolites in chemoprevention of cancer. J Cell Biochem 22:236–246

    Article  CAS  Google Scholar 

  • Kligman AM (1988) Preventing, delaying, and repairing photoaged skin. Cutis 41:419–420

    PubMed  CAS  Google Scholar 

  • Kligman LH (1986) Photoaging. Manifestations, prevention, and treatment. Dermatol Clin 4:517–528

    PubMed  CAS  Google Scholar 

  • Krinsky NI (1994) Carotenoids and cancer: basic research studies. In: Frei B (ed) National antioxidants in human health and disease. Academic, San Diego, pp 239–261

    Google Scholar 

  • Kozuki Y, Miura Y, Yagasaki K (2000) Inhibitory effects of carotenoids on the invasion of rat ascites hepatoma cells in culture. Cancer Lett 151(1):111–115

    Article  PubMed  CAS  Google Scholar 

  • Mc Bride, Preston PD, Loeb LA (1991) Mutagenic spectrum resulting from DNA damage by oxygen radicals. Biochemistry 30:207–213

    Article  CAS  Google Scholar 

  • Millen AE, Tucker MA, Hartge P, Halpern A, Elder DE, Guerry D 4th, Holly EA, Sagebiel RW, Potischman N (2004) Diet and melanoma in a case-control study. Cancer Epidemiol Biomarkers Prev 13(6):1042–1051

    PubMed  CAS  Google Scholar 

  • Moysan A, Marquis I, Gaboriau F, Santus R, Dubertret L, Morliere P (1993) Ultraviolet A-induced lipid peroxidation and antioxidant defense systems in cultured human skin fibroblasts. J Invest Dermatol 100:692–698

    Article  PubMed  CAS  Google Scholar 

  • Narisawa T, Fukaura Y, Hasebe M, Michiko I, Aizawa R, Murakoshi M, Uemura S, Khachik F, Nishino H (1996) Inhibitory effects of natural carotenoids, ol-carotene, B-carotene, lycopene and lutein, on colonic aberrant crypt foci formation in rats. Cancer Lett 106:137–142

    Article  Google Scholar 

  • Oba A, Edwards C (2006) Relationships between changes in mechanical properties of the skin, wrinkling, and destruction of dermal collagen fiber bundles caused by photoaging. Skin Res Technol 4:283–288

    Article  Google Scholar 

  • Oh JH, Kim A, Park JM, Kim SH, Chung AS (2006) Ultraviolet B-induced matrix metalloproteinase-1 and -3 secretions are mediated via PTEN/Akt pathway in human dermal fibroblasts. J Cell Physiol 3:775–785

    Article  CAS  Google Scholar 

  • Pasquali-Ronchetti I, Baccarani-Contri M (1997) Elastic fiber during development and aging. Microsc Res Tech 38:428–435

    Article  PubMed  CAS  Google Scholar 

  • Petersen M, Hamilton T, Li HL (1995). Regulation and inhibition of collagenase expression by long-wavelength ultraviolet radiation in cultured human skin fibroblasts. Photochem Photobiol 62:444–448

    PubMed  CAS  Google Scholar 

  • Petersen MJ, Hansen C, Craig S (1992). Ultraviolet A irradiation stimulates collagenase production in cultured human fibroblasts. J Invest Dermatol 99:440–444

    Article  PubMed  CAS  Google Scholar 

  • Philips N, Burchill D, O’Donoghue D, Keller T, Gonzalez S (2004) Identification of benzene metabolites in dermal fibroblasts: regulation of cell viability, apoptosis, lipid peroxidation, and expression of MMP-1 and elastin by benzene metabolites. Skin Pharmacol Physiol 17:147–152

    Article  PubMed  CAS  Google Scholar 

  • Philips N, Devaney J (2003) Beneficial regulation of type I collagen and matrixmetalloproteinase-1 expression by estrogen, progesterone, and its combination in skin fibroblasts. J Am Aging Association 26:59–62

    CAS  Google Scholar 

  • Philips N, McFadden K (2004) Inhibition of transforming growth factor-beta and matrix metalloproteinases by estrogen, and prolactin in breast cancer cells. Cancer Lett 206:63–68

    Article  PubMed  CAS  Google Scholar 

  • Philips N, Smith J, Keller T, Gonzalez S (2003) Predominant effects of Polypodium leucotomos on membrane integrity, lipid peroxidation, and expression of elastin and matrixmetalloproteinase-1 in ultraviolet radiation exposed fibroblasts, and keratinocytes. J Dermatol Sci 32:1–9

    Article  PubMed  CAS  Google Scholar 

  • Philips N (2003) An anti TGF-b increased the expression of transforming growth factor-b, matrix metallproteinase-1, and elastin, and its effects were antagonized by ultraviolet radiation in epidermal keratinocytes. J Dermatol Sci 33:177–179

    Article  PubMed  CAS  Google Scholar 

  • Pratt S (1990) Dietary prevention of age-related macular degeneration. J Am Optom Assoc 70:39–47

    Google Scholar 

  • Preston D, Stern RS (1992) Non melanoma skin cancer of the skin. N Engl J Med 327:1649–1662

    Article  PubMed  CAS  Google Scholar 

  • Scharffetter-Kochanek K, Brenneisen P, Wenk J, Herrmann G, Ma W, Kuhr L, Keewes C, Wlaschek M (2000). Photoaging of the skin from phenotype to mechanisms. Exp Gerontol 35:307–316

    Article  PubMed  CAS  Google Scholar 

  • Scharffetter K, Wlaschek M, Hogg A, Bolsen K, Schothorst A, Goerz G, Krieg T, Plewig G (1991). UVA irradiation induces collagenase in human dermal fibroblasts in vitro and in vivo. Arch Dermatol Res 283:506–511

    Article  PubMed  CAS  Google Scholar 

  • Schwartz E, Gelfand JM, Mauch JC, Kligman LH (1998) Generation of a tropoelastin mRNA variant by alternative polyadenylation site selection in sun-damaged human skin and ultraviolet B-irradiated fibroblasts. Biochem Biophys Res Commun 246:217–221

    Article  PubMed  CAS  Google Scholar 

  • Slattery ML, Benson J, Curtin K, Khe-NI M, Schaeffer D, Potter JD (2000) Carotenoids and colon cancer. Am J Clin Nutr 71:575–582

    PubMed  CAS  Google Scholar 

  • Snodderly DM (1995) Evidence for protection against age-related macula degeneration by carotenoids and antioxidant vitamins. Am J Clin Nutr 62:1448S–1461S

    PubMed  CAS  Google Scholar 

  • Svobodova A, Walterova D, Vostalova (2006) Ultraviolet light induced alteration to the skin. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 150:25–38

    PubMed  CAS  Google Scholar 

  • Talvensaari-Mattila A, Paakko P, Hoyhtya M, Blance-Sequeiros G, Turpeenniemi-Hujanen T (1998). Matrix metalloproteinase-2 immunoreactive protein: a marker of aggressiveness in breast carcinoma. Cancer 83:1153–1162

    Article  PubMed  CAS  Google Scholar 

  • Toyoda M, Bhawan J (1995) Electron-microscopic observations of cutaneous photoaging versus intrinsic aging. J Geriatr Dermatol 3:131–143

    Google Scholar 

  • Tupet A, Lebreton-De Coster C, Dubertret L, Bernard C (1999) Low doses of ultraviolet A irradiation stimulate adhesion of human dermal fibroblasts by integrins in a protein kinase C-dependent pathway. J Photochem Photobiol 49:150–155

    Article  CAS  Google Scholar 

  • Wingerath T, Sies H, Stahl W (1998) Xanthophyll esters in human skin. Arch Biochem Biophys 355:271–274

    Article  PubMed  CAS  Google Scholar 

  • Werth VP, Williams KJ, Fisher EA, Bashir M, Rosenbloom J, Shi X (1997) UVB irradiation alters cellular responses to cytokines: role in extracellular matrix gene expression. J Invest Dermatol 108:290–294

    Article  PubMed  CAS  Google Scholar 

  • Wlaschek M, Briviba K, Stricklin GP, Sies H, Scharffetter-Kochanek K (1995). Singlet oxygen may mediate the ultraviolet A-induced synthesis of interstitial collagenase. J Invest Dermatol 104:194–198

    Article  PubMed  CAS  Google Scholar 

  • Wlaschek M, Heinen G, Poswig A, Schwarz A, Krieg T, Scharffetter-Kochanek K (1994). UVA-induced autocrine stimulation of fibroblast-derived collagenase/MMP-1 by interrelated loops of interleukin-1 and interleukin-6. Photochem Photobiol 59:550–556

    PubMed  CAS  Google Scholar 

  • Wlaschek M, Wenk J, Brenneisen P, Briviba K, Schwarz A, Sies H, Scharffetter-Kochanek K (1997). Singlet oxygen is an early intermediate in cytokine-dependent ultraviolet-A induction of interstitial collagenase in human dermal fibroblasts in vitro. FEBS Lett 413:539–542

    Article  Google Scholar 

  • Zeng G, McCue H, Mastrangelo L, Millis A (1996) Endogenous TGF-β activity is modified during cellular aging: effects on metalloproteinase and TIMP-l expression. Exp Cell Res 228:271–276

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Funding was provided partly by the Departments of Biology and Chemistry/Biochemistry of Georgian Court University, Lakewood, NJ.

Author information

Authors and Affiliations

  1. School of Science and Mathematics, Georgian Court University, Lakewood, NJ, USA

    Neena Philips, Thomas Keller, Cynthia Hendrix & Shannon Hamilton

  2. School of Natural Sciences, Fairleigh Dickinson University, Teaneck, NJ, USA

    Neena Philips, Rosemarie Arena & Marvin Tuason

  3. Dermatology, Massachussets General Hospital, Harvard Medical School, Boston, MA, 02114, USA

    Salvador Gonzalez

  4. Dermatology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Salvador Gonzalez

  5. University College, H-DH4-03, 1000 River Road, Teaneck, NJ, 07666, USA

    Neena Philips

Authors
  1. Neena Philips
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Keller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cynthia Hendrix
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shannon Hamilton
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rosemarie Arena
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marvin Tuason
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Salvador Gonzalez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neena Philips.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Philips, N., Keller, T., Hendrix, C. et al. Regulation of the extracellular matrix remodeling by lutein in dermal fibroblasts, melanoma cells, and ultraviolet radiation exposed fibroblasts. Arch Dermatol Res 299, 373–379 (2007). https://doi.org/10.1007/s00403-007-0779-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-007-0779-0

Keywords

Search

Navigation