Inhibitory Effects of Vitamin A and Its Derivatives on Cancer Cell Growth Not Mediated by Retinoic Acid Receptors

• Published in: Biological & pharmaceutical bulletin Vol. 45; no. 9; pp. 1213 - 1224
• Main Author: Takahashi, Noriko
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.09.2022; Japan Science and Technology Agency
• Subjects: Acute promyeloid leukemia; Antitumor activity; Antitumor agents; Cancer; cell growth inhibition; Clinical trials; Drug development; Esters; Food plants; Hepatocytes; Promyeloid leukemia; retinoic acid; Retinoic acid receptors; retinol; retinoylation; Stellate cells; Vitamin A; Vitamin E; β-Carotene
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b22-00315

Vitamin A is an important trace essential nutrient. Vitamin A is present as a retinyl ester in animal foods and as β-carotene (provitamin A), which is a precursor of vitamin A, in plant foods such as green and yellow vegetables. After ingestion and absorption in the body, these are converted into retinol and stored as retinyl esters in stellate cells in the liver. The stored retinyl esters are decomposed into retinol as needed, and converted into the aldehyde retinal, which plays an important role in vision. Retinoic acid (RA) has a variety of effects. In particular, RA is used as a therapeutic agent for acute promyelocytic leukemia. This review will cover (1) elucidation of anti-refractory cancer effects of retinol (vitamin A) not mediated by RA receptors, (2) elucidation of anti-cancer effects of RA not mediated by RA receptors and (3) the development of candidate new anti-cancer agents that combine the actions of RA and retinol. Lessons learned from these findings are that vitamin A has anti-cancer activity not mediated by RA receptors; that nutritional management of vitamin A leads to prevention and treatment of cancer, and that new compounds developed from RA derivatives represent good anti-cancer drug candidates that are in various stages of clinical trials.