Fundamentals of Cancer Prevention by David S. Alberts & Lisa M. Hess

Author:David S. Alberts & Lisa M. Hess
Language: eng
Format: epub
ISBN: 9783030159351
Publisher: Springer International Publishing

12.4.5.4 Nutritional Photoprotection

The dietary origin of numerous photochemopreventive factors suggests the possibility of achieving efficient skin delivery through oral systemic administration, an emerging concept referred to as “nutritional photoprotection.” Indeed, clinical studies document feasibility of human skin photoprotection by dietary intake of lycopene from processed tomato and flavonoid-rich cocoa (Sies and Stahl 2004; Heinrich et al. 2006; Williams et al. 2009). In addition, oral administration of non-dietary photoprotectants including aqueous extracts of polypodium leucotomos have given impressive clinical results, particularly in the context of attenuation of skin photo-hypersensitivity reactions (e.g., polymorphic light eruption) in human patients (Middelkamp-Hup et al. 2004; Gonzalez et al. 2010; Parrado et al. 2016). Photoprotective efficacy of nutritional intervention has been attributed to direct UV absorption by chromophores contained in phytochemicals such as conjugated polyenes in carotinoids or 2-phenylchromen-4-one in flavonoids (Astner et al. 2007). It should be mentioned that the degree of protection against acute solar insult achievable by nutritional intervention (as assessed by suppression of solar erythema) is generally moderate and does not reach the level of protection achieved by synthetic sunscreen agents. Moreover, safety concerns related to chronic administration of specific phytochemicals such as carotenoids at elevated oral doses have been raised. It has been demonstrated that systemic administration of the apocarotenoid bixin in SKH-1 mice, a key component of achiote (also referred to as “annatto”) and FDA-approved food colorant and spice used since ancient times throughout the tropical Americas, provides significant skin photoprotection and improvement of barrier integrity as a function of cutaneous NRF2 activation. Specifically, it was reported that (a) bixin, devoid of pro-vitamin A activity, is a potent activator of the NRF2-dependent cytoprotective response in human skin keratinocytes; (b) systemic administration of bixin activates NRF2 with protective effects against solar UV-induced skin damage; and (c) bixin-induced suppression of photodamage is observable in Nrf2+/+ but not in Nrf2−/− SKH-1 mice confirming the NRF2 dependence of bixin-induced antioxidant and anti-inflammatory effects that occur independent of photon absorption (Tao et al. 2015; Rojo de la Vega et al. 2017; Rojo de la Vega et al. 2018).

Importantly, molecular mechanisms beyond UV screening including excited state quenching, NRF2 activation of the cellular antioxidant response, inhibition of inflammatory signaling (NFκB, AP-1), modulation of energy metabolism and DNA repair, and attenuation of photoimmunosuppression may determine the photochemopreventive activity of diverse dietary biofactors that have shown efficacy in animal models and recent human trials (Afaq and Mukhtar 2006; Nichols and Katiyar 2010; Parrado et al. 2016; Minocha et al. 2017). Specifically, encouraging clinical data indicate the efficacy of oral nicotinamide for chemoprevention of nonmelanoma skin cancer as substantiated by a multicenter, phase 3, double-blind, randomized, placebo-controlled trial in a high-risk population (“Oral Nicotinamide to Reduce Actinic Cancer” [ONTRAC]), followed by clinical evidence indicating efficacy of nicotinamide-based skin cancer chemoprevention in renal transplant recipients (Chen et al. 2015, 2016).

More research is needed in order to substantiate feasibility and preventive benefits of dietary photoprotection aiming at an optimal cutaneous supply of specific phytochemicals and nutrients that increase constitutive skin defense against the deleterious consequences of acute and chronic UV exposure.

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