The Sunscreen ParadoxPopular Misconceptions About Skin Cancer PreventionJune 2006
By Steven V. Joyal, MD
The Best Skin-Protecting Topical Ingredients
Exciting recent research shows that, in addition to broad-spectrum UV-A and UV-B blocking ingredients, natural topical ingredients can help protect skin against free radical-generated damage induced by UV light. Such natural agents may offer protection against photoaging, hyperpigmentation, and skin cancers.
• Green tea extract (epigallocatechin gallate, or EGCG). Deriving the health benefits of green tea is not limited to drinking it or taking it in the form of a high-potency extract. Topical administration likewise provides great benefits, including protecting against damage that can contribute to skin cancer and skin aging.
EGCG, a prime component of green tea, provides broad-spectrum protection against UV light-induced DNA damage and immune system dysfunction of the skin.24,25 Topical green tea extract is exceptional in preventing the inflammation and oxidative stress associated with UV light-induced skin damage.26-31 As a result, scientists believe green tea may help prevent skin cancers that commonly result from exposure to the sun’s radiation.
Exciting data from validated models of skin cancer strongly suggest that topically applied green tea extract can reduce the incidence and size of skin tumors. Importantly, this protection occurred even when green tea was applied following (not just before) UV light-induced damage.32 Thus, green tea may not only help prevent damage from UV rays, but also may help repair damage that has already occurred.
EGCG’s benefits also include anti-aging effects. In aging human skin, topically applied green tea extract stimulates structural support cells in the skin called keratinocytes, leading to an increase in skin thickness. Furthermore, subsequent UV exposure fails to destroy these cells, suggesting that topical green tea provides a protective effect against UV light.33 Thus, green tea helps reverse two of the hallmarks of aging skin: reduced skin thickness and keratinocyte destruction. This suggests a central role for green tea in preventing skin aging and promoting youthful skin.
• Rosemary extract (ursolic and carnosic acids). The aromatic herb rosemary, used for thousands of years as both a spice and medicinal agent, is particularly rich in carnosic and ursolic acids, two potent antioxidant and anti-inflammatory agents. More than a decade ago, scientists found that carnosic and ursolic acids effectively prevent skin cancer in a validated model of human skin cancer carcinogenesis.34
Ursolic acid acts powerfully to inhibit the growth of cancerous melanoma cells.35 It also inhibits reactive oxygen species in skin cells and prevents damage from the skin-aging effects of UV-A light.36
In addition, research has demonstrated that when specially formulated with lipids, ursolic acid enhances the dermal collagen and ceramide content of normal human skin cells, which are called epidermal keratinocytes.37,38 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.
• Turmeric extract (tetrahydrocurcumin). Curcumin is fast becoming known as a cure-all nutrient, and for good reason. Derived from the pungent spice turmeric, curcumin has excellent anti-inflammatory and antioxidant properties. Curcumin inhibits cancer initiation and promotion in validated cancer models.39,40
Curcumin induces the powerful tumor suppressor gene p53 and promotes the death of basal cell skin cancer cells.41 Furthermore, research shows that curcumin can make mutant, treatment-resistant malignant melanoma cell lines more responsive to chemotherapy.42
While these and other studies suggest that topical curcumin may benefit the skin, the staining properties of its bright yellow native pigment have prevented its widespread use in topical products. Fortunately, a major metabolite of curcumin called tetrahydrocurcumin does not possess the staining characteristics of native curcumin, yet it demonstrates anti-cancer effects that are similar to those of native curcumin. In fact, validated skin cancer models have shown that tetrahydrocurcumin inhibits skin cancer promotion.43
Laboratory studies indicate that topical tetrahydrocurcumin is a safe and effective skin-lightening agent.44,45 Skin-lightening agents help fade sun-induced areas of hyperpigmentation, or skin darkening. Many such agents work by inhibiting tyrosinase, a key enzyme involved in melanin synthesis. Thus, the colorless turmeric root derivative tetra-hydrocurcumin may help protect the skin against the detrimental effects of UV light and may help prevent (or fade) hyperpigmented areas of skin. While hyperpigmentation is not a medically harmful condition, it is always advisable to have a physician examine new brown spots to rule out skin cancers.
• Milk thistle extract (silibinin). The milk thistle plant contains silibinin and silymarin, two compounds that are well known for their anti-oxidant, anti-inflammatory, and immune-enhancing properties in the context of liver disease. Less well known—but equally important—are the documented benefits of milk thistle extract against skin cancer.
Topical application of silymarin significantly decreased skin cancer number and size in a validated model of tumor promotion.46 These findings are supported by other studies that show similar effects for silibinin. For example, silibinin protects against UV light-induced DNA damage and cancer cell growth.47
Additionally, research shows that silibinin enhances the powerful tumor suppressor gene p53, a genetic factor that protects against cancer. Silibinin acts by other mechanisms to prevent UV light-induced skin cancer. In fact, some findings suggest that silibinin can help to repair DNA damage caused by previous exposure to UV light.48
Since milk thistle extract is well tolerated and acts in several ways to fight the cancer-causing effects of solar radiation, leading researchers believe it may be an ideal addition to sunscreen formulations.49
• Licorice root. The medicinal properties of licorice root have been known since ancient Greece and Rome.50 A powerful skin protectant, licorice has anti-inflammatory, immune-boosting, and anti-cancer effects, including protecting against DNA damage.51 Licorice extract also has demonstrated efficacy in treating atopic dermatitis, an allergy-related, intensely itchy swelling of the skin.52
Glycyrrhizin, the main component of licorice root, protects against UV-B light-induced damage in the context of human melanoma cells.53 Glycyrrhetinic acid, another constituent of licorice, protects against skin tumor initiation and promotion in a validated model of skin cancer.54
An extract of licorice called glabridin reduces inflammation resulting from UV light exposure. In fact, when a licorice extract rich in glabridin was applied to the skin before exposure to UV light, it helped prevent the redness and pigmentation that would normally have occurred. Licorice extract also reduces melanin synthesis, suggesting that it may have applications in preventing and fading unsightly “age spots,” or areas of hyper-pigmented skin.55
Furthermore, licorice extract’s antioxidant activity has been shown to enhance the stability of other compounds when added to a topical dermatological cream.56
The FDA’s sun protection factor (SPF) rating system is inherently flawed in that it measures the effectiveness of sunscreen products against UV-B light, but not against deeper-penetrating UV-A light. Unfortunately, despite the FDA’s public acknowledgment of this shortcoming back in 2000, the rating system has still not been changed.
Natural sunlight activates vitamin D in the skin, and vitamin D has extraordinary anti-cancer benefits. For those at greatest risk of skin cancer, consuming additional vitamin D may be a more appropriate strategy than additional sun exposure. Although there are many unusual theories about skin cancer in the medical literature, until these theories have more definitive proof, a cautious approach to sun exposure is indicated. For most of us, a prudent strategy suggests 10-15 minutes of exposure to natural sunlight two to three times weekly, with additional vitamin D supplementation as a reasonable option.
Natural topical products such as green tea extract, turmeric, and licorice root extract offer remarkable protection against premature skin aging and skin cancer that all too often result from excessive sun exposure and sunburn.
Your skin is designed to last a lifetime—treat it well, and it will!
1. Solar and ultraviolet radiation (IARC). Monographs on the evaluation of the carcinogenic risk of chemicals to humans. IARC. 1992;55.
2. Naylor MF, Farmer KC. The case for sunscreens. A review of their use in preventing actinic damage and neoplasia. Arch Dermatol. 1997 Sep;133(9):1146-54.
3. Available at: www.cancer.org/docroot/CRI/ content?CRI_2_4_1X-What_are_the_key_ statistics_for_melanoma_50.asp?sitearea. Accessed March 27, 2006.
4. Available at: www.fda.gov/FDAC/features/2000/400_sun.html. Accessed March 27, 2006.
5. 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.
6. Sakurai H, Yasui H, Yamada Y, Nishimura H, Shigemoto M. Detection of reactive oxygen species in the skin of live mice and rats exposed to UVA light: a research review on chemiluminescence and trials for UVA protection. Photochem Photobiol Sci. 2005 Sep;4(9):715-20.
7. Hanson KM, Clegg RM. Bioconvertible vitamin antioxidants improve sunscreen photoprotection against UV-induced reactive oxygen species. J Cosmet Sci. 2003 Nov;54(6):589-98.
8. Darr D, Dunston S, Faust H, Pinnell S. Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants. Acta Derm Venereol. 1996 Jul;76(4):264-8.
9. Available at: http://www.uspdqi.org/pubs/monographs/sunscreen_agents.pdf#search=’sunscreens%20and%20titanium%20dioxide%20and%20cinnamates%20and%20PABA’. Accessed March 27, 2006.
10. Krekels G, Voorter C, Kuik F, et al. DNA protection by sunscreens: p53 immunostaining. Eur J Dermatol. 1997;7(4):259-62.
11. Farmer KC, Naylor MF. Sun exposure, sunscreens, and skin cancer prevention: a year-round concern. Ann Pharmacother. 1996 Jun;30(6):662-73.
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. 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.
14. Smedby KE, Hjalgrim H, Melbye M, et al. Ultraviolet radiation exposure and risk of malignant lymphomas. J Natl Cancer Inst. 2005 Feb 2;97(3):199-209.
15. 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.
16. Grant, WB. A multifactor ecologic analysis of the geographic variation in cancer mortality rates in the USA. Cancer Causes & Control (submitted).
17. Devesa SS, Grauman MA, Blot, WJ, Pennello GA. Hoover RN, Fraumeni JF. Atlas of cancer mortality in the United States: 1950 to 1994. NIH. 1999:99:4564.
18. Kawa S, Nikaido T, Aoki Y, et al. Vitamin D analogues up-regulate p21 and p27 during growth inhibition of pancreatic cancer cell lines. Br J Cancer. 1997;76(7):884-9.
19. Verlinden L, Verstuyf A, Convents R, et al. Action of 1,25(OH)2D3 on the cell cycle genes, cyclin D1, p21 and p27 in MCF-7 cells. Mol Cell Endocrinol. 1998 Jul 25;142(1-2):57-65.
20. Liu M, Lee MH, Cohen M, Bommakanti M, Freedman LP. Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev. 1996 Jan 15;10(2):142-53.
21. Hutchinson PE, Osborne JE, Lear JT, et al. Vitamin D receptor polymorphisms are associated with altered prognosis in patients with malignant melanoma. Clin Cancer Res. 2000 Feb;6(2):498-504.
22. Holick MF. Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endocrinol Diabetes. 2002;9:87-98.
23. Robinson TA, Kligman AM. Treatment of solar keratoses of the extremities with retinoic acid and 5-fluorouracil. Br J Dermatol. 1975 Jun;92(6):703-6.
24. Katiyar SK, Elmets CA. Green tea polyphenolic antioxidants and skin photoprotection (Review). Int J Oncol. 2001 Jun;18(6):1307-13.
25. 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.
26. Katiyar SK. Skin photoprotection by green tea: antioxidant and immunomodulatory effects. Curr Drug Targets Immune Endocr Metabol Disord. 2003 Sep;3(3):234-42.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. 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.
39. 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.
40. Huang MT, Newmark HL, Frenkel K. Inhibitory effects of curcumin on tumorigenesis in mice. J Cell Biochem Suppl. 1997;27:26-34.
41. Jee SH, Shen SC, Tseng CR, Chiu HC, Kuo ML. Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells. J Invest Dermatol. 1998 Oct; 111(4):656-61.
42. Bush JA, Cheung KJ, Jr., Li G. Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53. Exp Cell Res. 2001 Dec 10;271(2):305-14.
43. Huang MT, Ma W, Lu YP, et al. Effects of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion. Carcinogenesis. 1995 Oct;16(10):2493-7.
44. Research Report, Sami Labs Ltd, 2002.
45. Research Report, Sabinsa Corporation, 2003.
46. 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.
47. 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.
48. Singh RP, Agarwal R. Mechanisms and preclinical efficacy of silibinin in preventing skin cancer. Eur J Cancer. 2005 Sep;41(13):1969-79.
49. Katiyar SK. Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects (review). Int J Oncol. 2005 Jan;26(1):169-76.
50. Fiore C, Eisenhut M, Ragazzi E, Zanchin G, Armanini D. A history of the therapeutic use of liquorice in Europe. J Ethnopharmacol. 2005 Jul 14;99(3):317-24.
51. Wang ZY, Nixon DW. Licorice and cancer. Nutr Cancer. 2001;39(1):1-11.
52. Saeedi M, Morteza-Semnani K, Ghoreishi MR. The treatment of atopic dermatitis with licorice gel. J Dermatolog Treat. 2003 Sep;14(3):153-7.
53. Rossi T, Benassi L, Magnoni C, et al. Effects of glycyrrhizin on UVB-irradiated melanoma cells. In Vivo. 2005 Jan;19(1):319-22.
54. Wang ZY, Agarwal R, Zhou ZC, Bickers DR, Mukhtar H. Inhibition of mutagenicity in Salmonella typhimurium and skin tumor initiating and tumor promoting activities in SENCAR mice by glycyrrhetinic acid: comparison of 18 alpha- and 18 beta-stereoisomers. Carcinogenesis. 1991 Feb;12(2):187-92.
55. 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.
56. 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.