This review focuses on the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX.
Astaxanthin (ATX), one of the most common carotenoids, is widely distributed in the red pigment of shrimp, salmon, crab and asteroidean. In 1999, it was approved for use as a dietary supplement. ATX shows more powerful anti-oxidative property than other carotenoids, such as canthaxanthin, lutein, zeaxanthin and β-carotene. It has been suggested that ATX could protect against neurotoxin or oxidative stress-induced damage both in vivo and in vitro. Previous researches have used ATX as an anti-oxidant therapeutic agent in models of brain injury and cardiovascular disease. Furthermore, at least 8 clinical studies have been conducted in cardiovascular disease to assess the dosing, bioavailability and safety of ATX. Notably, no significant side effects of ATX have been reported so far. In addition to its potent anti-oxidative effects, evidence suggests that ATX has anti-cancer efficacy in multiple types of cancer, including oral cancer, bladder carcinogenesis, colon carcinogenesis, leukemia and hepatocellular carcinoma. The anti-cancer effects of ATX are reportedly attributed to its effects on the pathological process of cancer cells through a variety of pathways including apoptosis, inflammation and cell junction.
ATX exhibits an obvious anti-proliferative effect in cancers. Furthermore, several studies indicated that the normal cells were unaffected/less affected than cancer cells by ATX.
The role of inflammation in the development of cancer was firstly described by Rudolf Virchow in 1863. Since inflammation affects all stages of cancer, for example, increasing the onset risk, starting the initial genetic mutation, supporting tumor progression and promoting invasion and metastasis, it could be the key target of ATX.
Invasion and migration are two pivotal processes in the development of cancer. To invade surrounding tissue and metastasize, malignant cancer cells break away from the primary tumor, attach to and degrade proteins that make up the surrounding extracellular matrix. Then cancer cells escape the original tumor site and migrate to other parts of the body via the lymphatic system, bloodstream or by direct extension.
Thus, by inhibiting invasion factors, ATX may be valuable in preventing cancer cell invasion and metastasis.
As a fat soluble compound, ATX also follows the same intestinal absorption path as dietary fat. Absorption of ATX is affected by the same factors that influence fat absorption. When ATX is fed to human subjects, detailed pharmacokinetic data are difficult to obtain for single doses of less than 10 mg, due to limitations of assay precision. However, there is good data to indicate a single 10 mg dose can persist in the blood for 24 h and a 100 mg dose for 76 h. Doses as low as 1 mg can significantly increase blood levels when taken once daily for four weeks.
A growing number of studies show that ATX emerges as a key player in cancer therapy. It also influences a multitude of molecular and cellular processes. These observations make ATX an attractive therapeutic agent for developing novel treatment protocols, and possibly for combining with other chemotherapeutics to overcome drug resistance and achieve better outcomes. Ultimately, ATX may hold promise for clinical cancer therapy.
