Anti-tumor activity of astaxanthin on Meth-A tumor cells and its mode of action

Astaxanthin, a xanthophyll in seafood accumulates in tissues and has potent anti-tumor activity in rodent models. We examined the anti-tumor activity of astaxanthin with methylcholanthrene-induced (Meth-A) tumor cells (BALB/c background) both in vivo and in vitro. Meth-A tumor cells grown in astaxanthin (10 ^-8 to 10 ^-10 mol/L) supplemented medium had lower cell numbers and less DNA synthesis (BrdU assay) at 1-2 days post-incubation than control cultures. It did not alter LDH release (a marker for necrosis) and apoptotic changes, indicating that astaxanthin acts by inhibiting in vitro proliferation of Meth-A tumor cells. Astaxanthin (0.01 to 0.04% of the diet) was fed to tumor-inoculated BALB/c mice (5-10 x 10 ⁵ cells subcutaneously) following inoculation with Meth-A tumor cells. Dietary astaxanthin inhibited tumor growth in a dose dependent manner which also correlated with serum astaxanthin concentrations. Also, astaxanthin may modulate immune responses against Meth-A tumor cells which express tumor antigens. Tumor-inoculated mice developed significant cytotoxic T lymphocyte (CTL) activity and IFNγ production by tumor-draining lymph node (TDLN) and spleen cells at 2-3 weeks following inoculation. However, diets supplemented with astaxanthin induced higher CTL activity and IFNγ production by TDLN and spleen cells against Meth-A tumor cells than mice fed a control diet. Astaxanthin may attenuate tumor development through directly suppressing tumor cell proliferation and augmenting tumor immunity.