Astaxanthin Induces Mitochondria-Mediated Apoptosis in Rat Hepatocellular Carcinoma CBRH-7919 Cells

Abstract

The marine environment is usually characterized by highsalt, high pressure, low temperature, less or no illumination and poor nutrition. The marine organisms living under these conditions are well adapted to such adverse conditions, regardless of the size, shape, presence or absence of shells, and running fast or slow. Marine organisms have their own metabolism and defense systems which are different from terrestrial organisms in many ways. They produce a large number of metabolites with novel structures and potent activities.1-3) Since the 1960s, marine natural products have been considered as an attractive source for the discovery of new drugs to prevent and treat many human diseases including malignant tumors. Since the land resources are shrinking over the years at an alarming rate, scientists have predicted that the most promising anticancer drugs might be discovered from the marine biota. 4,5) Therefore, isolation of marine natural products and study of their pharmacological activities have attracted great interest.Astaxanthin was first isolated from lobsters in 1938, and since then it has been found in a diverse array of organisms such as shrimp, sea bream, crab, salmon, algae and other marine organisms. It is a member of the carotenoid family and the only known keto-carotenoid which can be transported into the brain by transcytosis through the hematoencephalic barrier.6,7) Its bioavailability can be enhanced in the presence of fat: the elimination half-life was 15.9Ϯ5.3 h (nϭ32). 8) Recent studies [9][10][11] have shown that astaxanthin has anticancer activity, which is attributed to its ability to trigger specific cellular immune response and its antioxidant activity. Jyonouchi et al. 12) investigated the pharmacological activity of astaxanthin by feeding astaxanthin containing diet to the mice with methylcholanthrene-induced fibrosarcoma and found that astaxanthin could significantly inhibit proliferation of tumor cells by stimulating the immune response against tumor antigens. Ishikawa et al. 10) reported inhibition of adult leukemia T-cell proliferation by feeding diets containing astaxanthin to mice harboring tumors induced by human T-cell leukemia virus type 1 (HTLV-1). They suggest that astaxanthin induced the arresting of cell cycle of infected T cells at G1 phase and apoptosis, thereby enhancing the anti-tumor immune response. In another report, 13) astaxanthin was shown to activate the pre-inflammatory gene product, nuclear factor-b, by blocking the inflammatory process. It also inhibits the generation of nitric oxide (NO) and prostaglandin E2, and promotes the effects of other factors such as pre-inflammatory cytokines, tumor necrosis factor-a and interleukin-b. However, the effect of astaxanthin on hepatoma cells and its mechanism have not yet been reported.In the present study, we showed that astaxanthin could induce apoptosis in rat hepatocellular carcinoma CBRH-7919 cells by altering the mitochondria metabolism. Experiments were designed to reveal the relationship between astaxanthin and...

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Neuroprotective Properties of the Marine Carotenoid Astaxanthin and Omega-3 Fatty Acids, and Perspectives for the Natural Combination of Both in Krill Oil

“…Moreover, based on the same evidence, apoptotic processes (especially from intrinsic mechanisms) would be remediated by ASTA treatments. Current wisdom on the relationship between ASTA and apoptosis shows conflicting anti- and pro-apoptotic results, depending on ASTA concentrations, cell types, and the concomitant presence of other antioxidants or anti-inflammatory agents [113,114,115,116]. These observations are not surprising due to the well-known dual chemical behavior of carotenoids, as described previously [84,85].…”