Standardized rosemary (Rosmarinus officinalis) extract induces Nrf2/sestrin-2 pathway in colon cancer cells

• Benefits to gastrointestinal health of rosemary extract, a natural food preservative, are proposed.
• The mechanism relies on the activation of Nrf2 signaling.
• An indirect activation of Nrf2 by activation of PERK is proposed.
• Carnosic acid is proposed to be one of the active ingredients in the rosemary extract.

Rosemary and its polyphenolic diterpene, carnosic acid, are known to possess antioxidant activity and are used as a natural antioxidant food preservative. The intake of vegetables and certain plant components has been reported to play a major role in promoting gastrointestinal health. In the current study, the anticancer activity of rosemary extract and carnosic acid was evaluated to understand the potential implications on gastrointestinal health. We also evaluated the anti-cancer activity of rosemary extract in a nude mouse model. Rosemary extract and carnosic acid, increased apoptosis, and decreased viability in colon cancer cell lines. Rosemary extract and carnosic acid significantly upregulated the expression of Nrf2 in colon cells and inhibited a HCT116 xenograft tumor formation in mice. These results are especially significant as rosemary extract is increasingly being incorporated into food products across the United States and Europe as a food preservative.