Anticancer Properties of Curcumin and Interactions With the Circadian Timing System

Abstract

The phytochemical curcumin is a major component of turmeric. It has recognized activity against cancer cells and affects several intracellular signaling pathways. Many molecules targeted by curcumin also regulate the circadian timing system that has effects on carcinogenesis, tumor growth, and metastasis. Although the circadian clock within cells may be suppressed in tumors, cancer cells are subjected to daily hormonal and neural activity that should be considered when timing optimal curcumin treatments. Rapid curcumin degradation in blood and tissues provides a challenge to maintaining sustained levels suitable for inducing cancer cell death, increasing the need to identify when during the circadian cycle rhythmically expressed molecular targets are present. Curcumin is well tolerated by individuals ingesting it for possible cancer prevention or in combination with conventional cancer therapies, and it shows low toxicity toward noncancerous cells at low dosages. In contrast, curcumin is particularly effective against cancer stem cells, which are treatment-resistant, aggressive, and tumor-initiating. Although curcumin has poor bioavailability, more stable curcumin analogs retain the anti-inflammatory, antioxidant, antimitotic, and pro-apoptotic benefits of curcumin. Anticancer properties are also present in congeners of curcumin in turmeric and after curcumin reduction by intestinal microbes. Various commercial curcuminoid products are highly popular dietary supplements, but caution is warranted. Although antioxidant properties of curcumin may prevent carcinogenesis, studies suggest curcumin interferes with certain chemotherapeutic agents. This review delves into the complex network of curcuminoid effects to identify potential anticancer strategies that may work in concert with daily physiological cycles controlled by the circadian timing system.