Preventing and Getting Rid of Skin Cancer with Resveratrol

New research suggests that resveratrol and other polyphenols from plants can help counteract the damaging effects on skin from the sun and other sources of toxic free radicals (e.g., inflammatory conditions). Too much sun exposure has been shown by numerous studies to be a primary factor in skin aging (e.g., wrinkles, hypo- and hyperpigmentation, dryness) and skin cancer. This is because the three types of ultraviolet (UV) radiation cause multiple negative biological effects in the skin:^12,166-167

Most of the UV radiation that reaches our skin is UVA (95%), followed by UVB. Even though UVB is far less prevalent, it is considered more toxic to DNA and 1000 times more likely to cause sunburn. However, UVA damage has been associated with 67% of rare skin cancers. Interestingly, animal studies suggest that UVA’s effect on the immune system may depend on a person’s genetics.¹⁶⁷

Although the skin has many protective mechanisms against UV damage, the combination of chronic exposure and UV’s immunosuppressant effects can overwhelm the skin’s natural defenses.¹² UV radiation also breaks down the enzyme catalase, an important antioxidant which neutralizes free radicals and other potentially damaging molecules (e.g., hydrogen peroxide) in the skin.¹⁶⁶

In addition, as we age the ends of the DNA strands (telomeres) get shorter, making our cells more susceptible to dysfunction or cell death. DNA damage from all these factors causes other changes at the cellular level that can promote cancer and skin aging, such as:¹⁶⁶

• lower levels of tumor-suppressing proteins
• dysfunctional regulation of growth factors which promotes out-of-control cancerous cell growth
• loss of regenerative skin cells
• defective DNA-repair mechanisms

Skin cancer is common and usually curable—depending on type and when it is caught. Malignant skin lesions can basically be grouped into one of two categories—melanoma and non-melanoma (e.g., basal cell and squamous cell carcinoma). The rarer melanoma group is considered more likely to spread, is virtually incurable at later stages because it is resistant to systemic cancer treatment, and is unfortunately on the rise worldwide.¹⁶⁸

Given the prevalence of all skin cancers and the poor prognosis of melanomas, researchers are consistently looking for safe preventive and therapeutic substances in addition to the conventional methods (e.g., sunscreen for prevention and chemotherapy and surgery for treatment). For example, scientists are exploring the use of botanical compounds such as resveratrol to prevent initial development, progression of premalignant lesions, and recurrence of melanoma in patients where it was caught early enough to be surgically removed.¹⁶⁸ There are even sunscreen and moisturizing skin products on the market which contain resveratrol specifically for its antioxidant protective qualities against UV sun damage. As for cancer therapy, resveratrol may offer hope even for the more deadly melanomas, including uveal melanoma.¹⁶⁹

How Does Resveratrol Work to Prevent or Treat Skin Cancer?

An extensive scientific literature search found one lab study from 2005 which reported that resveratrol combined with UVA exposure produced significant DNA damage and skin cell death.(34) DNA lesions are caused by changes in DNA bases either directly or in the presence of oxidative stress and are thought to be the precursors to cancer.^167,170 In this particular study, the researchers stated that resveratrol increased UVA mutations to the guanine DNA bases, as measured by increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine, and caused more DNA strand breaks.³⁴

However, it is difficult to reconcile these 2005 results with the multitude of studies that indicate the opposite, including:

• Resveratrol lowered plasma levels of the same type of DNA guanine base mutations in a 2009 animal study involving whole-body irradiation.¹⁷¹
• In two studies (from 2006 and 2010) on the same HaCaT-type skin cells and UVA, resveratrol administered in concentrations between 0-10 mg/l protected skin cells from UVA-induced DNA damage.^172-173

One possible explanation for the conflicting results could be the concentration of resveratrol used. The authors of the 2010 resveratrol-UVA study indicated that the difference in results could have been due to the much higher concentrations used in the 2005 study showing DNA damage from resveratrol and UVA.¹⁷²

UVA causes DNA base mutations indirectly through free radical damage, due to its wavelength, and animal studies indicate that resveratrol neutralizes both ROS and RNS free radicals.^167,170 As for DNA breaks, studies show that these may actually not be cancer-initiators.¹⁷⁰

Numerous lab and animal studies demonstrate that resveratrol protects skin cells against cell and DNA damage and skin cancer by decreasing cancer-promoting proteins stimulated by UVB, UVA, and toxins—all while increasing protective and tumor-suppressing factors. In fact, scientists at the University of Texas Health Science Center are testing resveratrol and other botanical substances that can supplement external sunscreen protection and help prevent cancer. Using mice that are genetically more prone to UV skin damage and cancer, these researchers have found that combining plant substances (e.g., resveratrol with grape seed extract) may be particularly beneficial for people at the greatest risk of skin and other cancers involving similar cells. People at high risk for these types of cancers include smokers, former smokers, and habitual sun-bathers with heavy tans—because their cells are already primed to change into malignancies.¹⁷⁴

Studies show that resveratrol’s anti-inflammatory and antioxidant properties counteract the effects of UV radiation. In basic terms, some of the ways that resveratrol works to prevent skin cancer is by neutralizing the free radicals or inhibiting the inflammatory proteins that UV stimulates.¹² When investigating how resveratrol binds to skin cells, researchers discovered that resveratrol helps promote skin healing factors and activates one of the body’s own powerful antioxidant enzymes (glutathione peroxidase).¹⁷⁶ Other researchers recently found that resveratrol activates another potent antioxidant protein called NF-E2-related factor-2 and protects skin cells against oxidative stress from UVA radiation.¹⁸⁸ It also appears to prevent mitochondrial dysfunction in skin cells related to skin damage from UVB.¹⁷⁶

Results of one study suggest that the beneficial effects of resveratrol are further stimulated by UVB exposure from the sun itself. Lab and animal studies suggest that resveratrol, in combination with UVB, significantly enhanced cancer cell death and inhibited further cancer growth. Evidence collected points to a variety of mechanisms that explain these effects, possibly by increasing receptivity of the cancer cells to UVB and/or interfering with biologically protective mechanisms that are activated in response to UVB presence.¹⁸¹