Moisturization, AQP-3 and Carcinoma Resistance

Posted: July 15, 2008

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By comparing the skin hydration levels of normal mice and AQP-3 knockout mice, it is revealed that the skin of mice lacking AQP-3 is dry and not elastic. Interestingly, if you measure the level of glycerin, these levels are significantly reduced in the absence of AQP-3. In short, AQP-3 is "good for you" and there has been an emergence of new cosmetic ingredients that stimulate AQP-3 expression, which (should) result in more skin hydration.

In the described study, it was observed that wounds in AQP-3 deficient mice healed significantly slower due to the role of AQP-3 in the proliferation of keratinocytes during wound healing; however, its involvement in skin tumorigenesis raised eyebrows. It was also shown that AQP-3 was strongly over-expressed in basal cells in human skin squamous cell carcinomas. Moreover, AQP-3 knockout mice do not develop skin tumors following exposure to a tumor initiator and phorbol ester promoter, a well-established multistage carcinogenesis model.

Subsequently, in May 2008, Alan Verkman published “A Cautionary Note on Cosmetics Containing Ingredients that Increase Aquaporin-3 Expression” in Experimental Dermatology in which he states, “Though the available data show prevention of skin tumorigenesis with AQP-3 deletion, it is not unreasonable to postulate an increased propensity for tumor formation when AQP-3 expression is upregulated. Further studies are thus indicated in testing the relation between epidermal AQP-3 upregulation and skin tumorigenesis as well as epidemiological evaluation of the incidence of squamous cell carcinomas and other skin cancers in subjects using cosmetics containing AQP-3 expression-enhancing ingredients.”

While Verkman is correct, the issue here surrounds the famous question: Which came first, the chicken or the egg? If there is more AQP-3 in basal squamous cell carcinoma, it does not automatically mean that increased AQP-3 levels lead to basal squamous cell carcinoma; i.e., every cow is an animal, but not every animal is a cow. Just as squamous cell carcinoma is associated with increased AQP-3 it does not automatically mean that increased AQP-3 leads to more squamous cell carcinoma—it could, but as Verkman says, more investigation is needed. He adds, “Perhaps, cosmetic testing in animals, which has fallen into disfavor among cosmetic companies and regulatory agencies, should be reinstituted at least in selected cases such as this.”

Although this idea is quite controversial, it may be better than launching a product and promoting it as a moisturizer that allows the body to produce approximately 50% less AQP-3. Making a claim that skin is more resistant against cancer is clearly medical. Let’s do the science properly and completely before we come up with new claims and completely confuse ourselves, our regulatory bodies and our consumers.