Life Extension Blood Test Super Sale

Life Extension Magazine

LE Magazine June 2005
image

Why Sunscreens Do Not Fully Prevent Skin Cancer

By Dale Kiefer

Licorice (Glycyrrhiza Glabra)

Licorice Extract and Rosemary

Licorice, derived from the roots of Glycyrrhiza glabra, has been used medicinally for more than 4,000 years. Modern science has confirmed that licorice is a powerful skin protectant. Numerous studies suggest that licorice extract protects the skin from the damaging effects of UV light.73,74 Licorice extract also has demonstrated efficacy in treating atopic dermatitis, an allergy-related, intensely itchy swelling of the skin.75

In animal studies, a preparation containing 0.5% glabridin, one of the primary active constituents in licorice extract, prevented the redness and inflammation normally associated with UV exposure when pre-applied to the skin. Licorice extract also reduces melanin synthesis.74 Recent research suggests that UV-induced DNA damage and subsequent repair efforts precede melanin synthesis.11 Furthermore, licorice extract’s antioxidant activity has been shown to enhance the stability of other compounds when added to a topical dermatological cream.76 This antioxidant activity evidently protects skin against damage caused by free radical and reactive oxygen species.73

Rosemary (Rosmarinus officinalis), a fragrant evergreen perennial herb, has been used as a seasoning and medicinal herb for several millennia. Rosemary contains numerous beneficial compounds, including cancer-fighting chemicals, antioxidants, and anti-inflammatory agents.77-79 At least two of these, carnosic acid and ursolic acid, are especially beneficial to skin.80-82 Application of rosemary extract has been shown to prevent chemically induced skin tumors in a mouse model of human skin cancer. Depending on the concentration of the extract, tumors were inhibited by up to 99%.80

Rosemary (Rosmarinus Officinalis)

Earlier this year, French researchers demonstrated that ursolic acid, derived from rosemary, significantly inhibited the proliferation of melanoma cells in culture, apparently by promoting apoptosis (programmed cell death).82 More than a decade earlier, Rutgers University scientists demonstrated that in a mouse model of human skin cancer, both carnosic and ursolic acids markedly inhibit tumor growth when applied to the skin.80 Korean scientists have shown that “ursolic acid significantly suppressed the UVA-induced reactive oxygen species production and lipid peroxidation” in a human keratinocyte culture. They concluded that ursolic acid “may be useful in the prevention of UVA-induced photoaging.”83 In addition, research has demonstrated that when specially formulated with lipids, ursolic acid enhances the dermal collagen and ceramide content of normal human epidermal keratinocytes.84,85 Collagen provides the “skeleton” that gives shape and structure to the skin, while ceramide is a lipid that helps maintain proper immune function, as well as youthful moisture content, in the skin. Keratinocytes make up as much as 95% of epidermal tissues and are responsible for producing keratin, the tough protein that contributes to healthy hair, nails, and skin.

Conclusion

When it comes to protecting yourself against skin cancer, the most common of cancers worldwide, sunscreen agents such as zinc oxide alone may not be enough. While sunscreens can help shield against UV light-induced sunburn, it is crucial to also protect the skin against the free radicals generated by solar radiation. Left unchecked, these notoriously harmful agents may contribute to skin aging, DNA damage, and skin cancer.

Fortunately, a number of powerful plant-derived phytochemicals may help protect the skin via novel mechanisms that are distinct from those provided by sunscreen agents. Emerging evidence suggests that topically applied botanicals—including green tea, milk thistle, grape seed, turmeric root, licorice root, and rosemary—may prevent deleterious effects from sun exposure such as inflammation, DNA damage, immune deficits, skin aging, and cancer. The potent antioxidant properties of these plant extracts may account for their skin-protective actions.

The combination of sunscreen agents with botanical extracts may thus provide the most complete protection against the harmful effects of UV light, by both screening solar rays and preventing the formation of damaging free radicals. These combinations offer promise not only in helping to guard against skin cancers but also in promoting healthy, youthful skin.

References

1. Dennis LK, Beane Freeman LE, VanBeek MJ. Sunscreen use and the risk for melanoma: a quantitative review. Ann Int Med. 2003 Dec 16;139(12):966-78.

2. Haywood R, Wardman P, Sanders R, Linge C. Sunscreens inadequately protect against ultraviolet-A-induced free radicals in skin: implications for skin aging and melanoma? J Invest Dermatol. 2003 Oct;121(4):862-8.

3. Gasparro FP. Sunscreens, skin photobiology, and skin cancer: the need for UVA protection and evaluation of efficacy. Environ Health Perspect. 2000 Mar;108 Suppl 1:71-8.

4. Dangoisse C. Dermo-cosmetics and prevention of skin aging. Rev Med Brux. 2004 Sep;25(4):A365-70.

5. Greinert R, Volker B, Wende A, Voss S, Breitbart EW. Prevention of skin cancer. Necessity, implementation and success. Hautarzt. 2003 Dec;54(12):1152-63.

6. Schober-Flores C. The sun’s damaging effects. Dermatol Nurs. 2001 Aug;13(4):279-86.

7. Savona MR, Jacobsen MD, James R, Owen MD. Ultraviolet radiation and the risks of cutaneous malignant melanoma and non-melanoma skin cancer: perceptions and behaviours of Danish and American adolescents. Eur J Cancer Prev. 2005 Feb;14(1):57-62.

8. Available at: http://seer.cancer.gov/csr/1975_2001/results_merged/sect_16_melanoma.pdf. Accessed March 31, 2005.

9. Geller AC, Rutsch L, Kenausis K, Selzer P, Zhang Z. Can an hour or two of sun protection education keep the sunburn away? Evaluation of the Environmental Protection Agency’s Sunwise School Program. Environ Health. 2003 Nov 3;2(1):13.

10. Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_melanoma_50.asp?sitearea. Accessed March 31, 2005.

11. Agar N, Young AR. Melanogenesis: a photoprotective response to DNA damage? Mutat Res. 2005 Apr 1;571(1-2):121-32.

12. Mitchnick MA, Fairhurst D, Pinnell SR. Microfine zinc oxide (Z-cote) as a photostable UVA/UVB sunblock agent. J Am Acad Dermatol. 1999 Jan;40(1):85-90.

13. Wolf R, Matz H, Orion E, Lipozencic J. Sunscreens—the ultimate cosmetic. Acta Dermatovenerol Croat. 2003;11(3):158-62.

14. Prasad AS. Zinc: the biology and therapeutics of an ion. Ann Intern Med. 1996 Jul 15;125(2):142-4.

15. Kasperczyk S, Birkner E, Kasperczyk A, Zalejska-Fiolka J. Activity of superoxide dismutase and catalase in people protractedly exposed to lead compounds. Ann Agric Environ Med. 2004;11(2):291-6.

16. Kocaturk PA, Kavas GO, Erdeve O, Siklar Z. Superoxide dismutase activity and zinc and copper concentrations in growth retardation. Biol Trace Elem Res. 2004;102(1-3):51-9.

17. Tarnow P, Agren M, Steenfos H, Jansson JO. Topical zinc oxide treatment increases endogenous gene expression of insulin-like growth factor-1 in granulation tissue from porcine wounds. Scand J Plast Reconstr Surg Hand Surg. 1994 Dec;28(4):255-9.

18. Jin L, Murakami TH, Janjua NA, Hori Y. The effects of zinc oxide and diethyldithiocarbamate on the mitotic index of epidermal basal cells of mouse skin. Acta Med Okayama. 1994 Oct;48(5):231-6.

19. Diffey BL, Farr PM. Sunscreen protection against UVB, UVA and blue light: an in vivo and in vitro comparison. Br J Dermatol. 1991 Mar;124(3):258-63.

20. Farmer KC, Naylor MF. Sun exposure, sunscreens, and skin cancer prevention: a year-round concern. Ann Pharmacother. 1996 Jun;30(6):662-73.

21. Krekels G, Voorter C, Kuik F, et al. DNA protection by sunscreens: p53 immunostaining. Eur J Dermatol. 1997;7(4):259-62.

22. Meadows T. Effect of various sunscreen combinations on a product’s SPF value. J Soc Cosmet Chem. 1990 Mar-Apr;41:141-6.

23. Saladi RN, Persaud AN. The causes of skin cancer: A comprehensive review. Drugs Today (Barc.). 2005 Jan;41(1):37-53.

24. Diffey B. Sunscreen isn’t enough. J Photochem Photobiol B. 2001 Nov 15;64(2-3):105-8.

25. Bech-Thomsen N, Wulf HC. Sunbathers’ application of sunscreen is probably inadequate to obtain the sun protection factor assigned to the preparation. Photdermatol Photoimmunol Photomed. 1992-3 Dec;9(6):242-4.

26. Stokes R, Diffey B. How well are sunscreen users protected? Photodermatol Photoimmunol Photomed. 1997 Oct-Dec;13(5-6):186-8.

27. Phillips TJ, Bhawan J, Yaar M, Bello Y, Lopiccolo D, Nash JF. Effect of daily versus intermittent sunscreen application on solar simulated UV radiation-induced skin response in humans. J Am Acad Dermatol. 2000 Oct;43(4):610-8.

28. Calvo MS, Whiting SJ, Barton CN. Vitamin D intake: a global perspective of current status. J Nutr. 2005 Feb;135(2):310-6.

29. Calvo MS, Whiting SJ, Barton CN. Vitamin D fortification in the United States and Canada: current status and data needs. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1710S-6S.

30. Egan KM, Sosman JA, Blot WJ. Sunlight and reduced risk of cancer: is the real story vitamin D? J Natl Cancer Inst. 2005 Feb 2;97(3):161-3.

31. Reichrath J, Girndt M, Tilgen W, Querings K. UV-exposition and vitamin-D: How much sunlight do we need? Exp Dermatol. 2005 Feb;14(2):153.

32. Berwick M, Armstrong BK, Ben Porat L, et al. Sun exposure and mortality from melanoma. J Natl Cancer Inst. 2005 Feb 2;97(3):195-9.

33. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1678S-88S.

34. Miyako K, Kinjo S, Kohno H. Vitamin D deficiency rickets caused by improper lifestyle in Japanese children. Pediatr Int. 2005 Apr;47(2):142-6.

35. Strickland FM, Kuchel JM, Halliday GM. Natural products as aids for protecting the skin’s immune system against UV damage. Cutis. 2004 Nov;74(5 Suppl):24-8.

36. Katiyar SK, Elmets CA. Green tea polyphenolic antioxidants and skin photoprotection (review). Int J Oncol. 2001 Jun;18(6):1307-13.

37. Morley N, Clifford T, Salter L, et al. The green tea polyphenol (-)-epigallocatechin gallate and green tea can protect human cellular DNA from ultraviolet and visible radiation-induced damage. Photodermatol Photoimmunol Photomed. 2005 Feb;21(1):15-22.

38. Katiyar SK. Skin photoprotection by green tea: antioxidant and immunomodulatory effects. Curr Drug Targets Immune Endocr Metabol Disord. 2003 Sep;3(3):234-42.

39. Vayalil PK, Mittal A, Hara Y, Elmets CA, Katiyar SK. Green tea polyphenols prevent ultraviolet light-induced oxidative damage and matrix metalloproteinases expression in mouse skin. J Invest Dermatol. 2004 Jun;122(6):1480-7.

40. Katiyar SK, Mukhtar H. Green tea polyphenol (-)-epigallocatechin-3-gallate treatment to mouse skin prevents UVB-induced infiltration of leukocytes, depletion of antigen-presenting cells, and oxidative stress. J Leukoc Biol. 2001 May;69(5):719-26.

41. Vayalil PK, Elmets CA, Katiyar SK. Treatment of green tea polyphenols in hydrophilic cream prevents UVB-induced oxidation of lipids and proteins, depletion of antioxidant enzymes and phosphorylation of MAPK proteins in SKH-1 hairless mouse skin. Carcinogenesis. 2003 May;24(5):927-36.

42. Mittal A, Piyathilake C, Hara Y, Katiyar SK. Exceptionally high protection of photocarcinogenesis by topical application of (-)-epigallocatechin-3-gallate in hydrophilic cream in SKH-1 hairless mouse model: relationship to inhibition of UVB-induced global DNA hypomethylation. Neoplasia. 2003 Nov;5(6):555-65.

43. Elmets CA, Singh D, Tubesing K, et al. Cutaneous photoprotection from ultraviolet injury by green tea polyphenols. J Am Acad Dermatol. 2001 Mar;44(3):425-32.

44. Katiyar SK, Afaq F, Perez A, Mukhtar H. Green tea polyphenol (-)-epigallocatechin-3-gallate treatment of human skin inhibits ultraviolet radiation-induced oxidative stress. Carcinogenesis. 2001 Feb;22(2):287-94.

45. Katiyar SK, Bergamo BM, Vyalil PK, Elmets CA. Green tea polyphenols: DNA photodamage and photoimmunology. J Photochem Photobiol B. 2001 Dec 31;65(2-3):109-14.

46. Lu YP, Lou YR, Xie JG, et al. Topical applications of caffeine or (-)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice. Proc Natl Acad Sci USA. 2002 Sep 17;99(19):12455-60.

47. Chung JH, Han JH, Hwang EJ, et al. Dual mechanisms of green tea extract (EGCG)-induced cell survival in human epidermal keratinocytes. FASEB J. 2003 Oct;17(13):1913-5.

48. Katiyar SK. Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects (review). Int J Oncol. 2005 Jan;26(1):169-76.

49. Lahiri-Chatterjee M, Katiyar SK, Mohan RR, Agarwal R. A flavonoid antioxidant, silymarin, affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model. Cancer Res. 1999 Feb 1;59(3):622-32.

50. Katiyar SK, Roy AM, Baliga MS. Silymarin induces apoptosis primarily through a p53-dependent pathway involving Bcl-2/Bax, cytochrome c release, and caspase activation. Mol Cancer Ther. 2005 Feb;4(2):207-16.

51. Singh RP, Dhanalakshmi S, Agarwal C, Agarwal R. Silibinin strongly inhibits growth and survival of human endothelial cells via cell cycle arrest and downregulation of survivin, Akt and NF-kappaB: implications for angioprevention and antiangiogenic therapy. Oncogene. 2005 Feb 10;24(7):1188-202.

52. Mallikarjuna G, Dhanalakshmi S, Singh RP, Agarwal C, Agarwal R. Silibinin protects against photocarcinogenesis via modulation of cell cycle regulators, mitogen-activated protein kinases, and Akt signaling. Cancer Res. 2004 Sep 1;64(17):6349-56.

53. Li LH, Wu LJ, Zhou B, et al. Silymarin prevents UV irradiation-induced A375-S2 cell apoptosis. Biol Pharm Bull. 2004 Jul;27(7):1031-36.

54. Dhanalakshmi S, Mallikarjuna GU, Singh RP, Agarwal R. Dual efficacy of silibinin in protecting or enhancing ultraviolet B radiation-caused apoptosis in HaCaT human immortalized keratinocytes. Carcinogenesis. 2004 Jan;25(1):99-106.

55. Singh RP, Agarwal R. Flavonoid antioxidant silymarin and skin cancer. Antioxid Redox Signal. 2002 Aug;4(4):655-63.

56. Singh RP, Tyagi AK, Zhao J, Agarwal R. Silymarin inhibits growth and causes regression of established skin tumors in SENCAR mice via modulation of mitogen-activated protein kinases and induction of apoptosis. Carcinogenesis. 2002 Mar;23(3):499-510.

57. Bhatia N, Agarwal C, Agarwal R. Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells. Nutr Cancer. 2001;39(2):292-9.

58. Singh RP, Agarwal R. A cancer chemopreventive agent, silibinin targets mitogenic and survival signaling in prostate cancer. Mutat Res. 2004 Nov 2;555(1-2):21-32.

59. Chu SC, Chiou HL, Chen PN, Yang SF, Hsieh YS. Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Mol Carcinog. 2004 Jul;40(3):143-9.

60. Tyagi A, Agarwal C, Harrison G, Glode LM, Agarwal R. Silibinin causes cell cycle arrest and apoptosis in human bladder transitional cell carcinoma cells by regulating CDKI-CDK-cyclin cascade, and caspase 3 and PARP cleavages. Carcinogenesis. 2004 Sep;25(9):1711-20.

61. Bauer JH, Goupil S, Garber GB, Helfand SL. An accelerated assay for the identification of lifespan-extending interventions in Drosophila melanogaster. Proc Natl Acad Sci USA. 2004 Aug 31;101(35):12980-5.

62. Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. 2005 Mar 4.

63. Douillet-Breuil AC, Jeandet P, Adrian M, Bessis R. Changes in the phytoalexin content of various Vitis spp. in response to ultraviolet C elicitation. J Agric Food Chem. 1999 Oct;47(10):4456-61.

64. Roy AM, Baliga MS, Elmets CA, Katiyar SK. Grape seed proanthocyanidins induce apoptosis through p53, Bax, and caspase 3 pathways. Neoplasia. 2005 Jan;7(1):24-36.

65. Mittal A, Elmets CA, Katiyar SK. Dietary feeding of proanthocyanidins from grape seeds prevents photocarcinogenesis in SKH-1 hairless mice: relationship to decreased fat and lipid peroxidation. Carcinogenesis. 2003 Aug;24(8):1379-88.

66. Zhao J, Wang J, Chen Y, Agarwal R. Anti-tumor-promoting activity of a polyphenolic fraction isolated from grape seeds in the mouse skin two-stage initiation-promotion protocol and identification of procyanidin B5-3’-gallate as the most effective antioxidant constituent. Carcinogenesis. 1999 Sep;20(9):1737-45.

67. Shi J, Yu J, Pohorly JE, Kakuda Y. Polyphenolics in grape seeds-biochemistry and functionality. J Med Food. 2003;6(4):291-9.

68. Phan TT, See P, Lee ST, Chan SY. Protective effects of curcumin against oxidative damage on skin cells in vitro: its implication for wound healing. J Trauma. 2001 Nov;51(5):927-31.

69. Huang MT, Newmark HL, Frenkel K. Inhibitory effects of curcumin on tumorigenesis in mice. J Cell Biochem Suppl. 1997;27:26-34.

70. Research Report #786, Sabinsa Corporation, 1998.

71. Research Report, Sami Labs Ltd, 2002.

72. Research Report, Sabinsa Corporation, 2003

73. Di Mambro VM, Fonseca MJ. Assays of physical stability and antioxidant activity of a topical formulation added with different plant extracts. J Pharm Biomed Anal. 2005 Feb 23;37(2):287-95.

74. Yokota T, Nishio H, Kubota Y, Mizoguchi M. The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation. Pigment Cell Res. 1998 Dec;11(6):355-61.

75. Saeedi M, Morteza-Semnani K, Ghoreishi MR. The treatment of atopic dermatitis with licorice gel. J Dermatolog Treat. 2003 Sep;14(3):153-7.

76. Morteza-Semnani K, Saeedi M, Shahnavaz B. Comparison of antioxidant activity of extract from roots of licorice (Glycyrrhiza glabra L.) to commercial antioxidants in 2% hydroquinone cream. J Cosmet Sci. 2003 Nov;54(6):551-8.

77. Ho CT, Wang M, Wei GJ, Huang TC, Huang MT. Chemistry and antioxidative factors in rosemary and sage. Biofactors. 2000;13(1-4):161-6.

78. Calabrese V, Scapagnini G, Catalano C, et al. Biochemical studies of a natural antioxidant isolated from rosemary and its application in cosmetic dermatology. Int J Tissue React. 2000;22(1):5-13.

79. Baricevic D, Sosa S, Della LR et al. Topical anti-inflammatory activity of Salvia officinalis L. leaves: the relevance of ursolic acid. J Ethnopharmacol. 2001 May;75(2-3):125-32.

80. Huang MT, Ho CT, Wang ZY, et al. Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. Cancer Res. 1994 Feb 1;54(3):701-8.

81. Offord EA, Gautier JC, Avanti O, et al. Photoprotective potential of lycopene, beta-carotene, vitamin E, vitamin C and carnosic acid in UVA-irradiated human skin fibroblasts. Free Radic Biol Med . 2002 Jun 15;32(12):1293-303.

82. Harmand PO, Duval R, Delage C, Simon A. Ursolic acid induces apoptosis through mitochondrial intrinsic pathway and caspase-3 activation in M4Beu melanoma cells. Int J Cancer. 2005 Mar 10;114(1):1-11.

83. Soo LY, Jin DQ, Beak SM, Lee ES, Kim JA. Inhibition of ultraviolet-A-modulated signaling pathways by asiatic acid and ursolic acid in HaCaT human keratinocytes. Eur J Pharmacol. 2003 Aug 29;476(3):173-8.

84. Both DM, Goodtzova K, Yarosh DB, Brown DA. Liposome-encapsulated ursolic acid increases ceramides and collagen in human skin cells. Arch Dermatol Res. 2002 Jan;293(11):569-75.

85. Yarosh DB, Both D, Brown D. Liposomal ursolic acid (merotaine) increases ceramides and collagen in human skin. Horm Res. 2000;54(5-6):318-21.