Annatto Component Prevents UV Damage and Prevents Skin Cancer in Mouse Model

The apocarotenoid compound bixin is a widely consumed food additive that was shown in a recent paper to have potent antioxidant properties, which prevented the formation of cancer cells and skin damage from UV radiation in a mouse model.

Apocarotenoids are organic compounds derived from carotenoids by oxidative cleavage, catalyzed by carotenoid oxygenases. Examples include the vitamin A retinoids retinal, retinoic acid, and retinol; and the plant hormone abscisic acid.

Investigators at the University of Arizona (Tucson, USA) based their research on recent studies that suggested a photoprotective role of gene expression in skin cells orchestrated by the transcription factor Nrf2 (nuclear factor-E2-related factor 2). They explored the molecular mechanism underlying carotenoid-based systemic skin photoprotection in the SKH-1 mouse model.

A group of SKH-1 mice were injected with bixin, a [US] Food and Drug Administration approved compound found in annatto. Annatto is an orange-red condiment and food coloring derived from the seeds of the achiote tree (Bixa orellana). It is often used to impart a yellow or orange color to foods, but sometimes also for its flavor and aroma. The color of annatto comes from various carotenoid pigments, mainly bixin and norbixin, found in the reddish waxy coating of the seeds. Annatto and its extracts are now widely used as a coloring agent in many processed food products.

Results published in the November 4, 2015, online edition of the journal Free Radical Biology and Medicine revealed that systemic administration of bixin suppressed skin photodamage by suppressing epidermal oxidative DNA damage and inflammatory responses in the mice.

The investigators found that bixin activated Nrf2 through the critical cysteine-151 sensor residue in Keap1 (Kelch-like ECH-associated protein 1). Under quiescent conditions, Nrf2 is anchored in the cytoplasm through binding to Keap1, which, in turn, facilitates the ubiquitination and subsequent proteolysis of Nrf2. Because Nrf2 activation leads to a coordinated antioxidant and anti-inflammatory response, and Keap1 represses Nrf2 activation, Keap1 has become a very attractive drug target.

DNA damage and inflammatory responses were suppressed in mice carrying the NRF2 gene but not in mice that lacked the gene, confirming the NRF2-dependence of bixin-based photoprotection.

Senior author Dr. Georg Wondrak, associate professor of pharmacology and toxicology at the University of Arizona, said, "This discovery is unique because bixin is a nutritional factor, not a sunscreen applied to the skin. It prevents UV skin damage from the inside out by inducing cells to make protective antioxidants and repair factors. The compound does not kill skin cancer cells, but prevents their forming in the first place."

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