Astaxanthin Augmented the Anti-Hepatocellular Carcinoma Efficacy of Sorafenib Through the Inhibition of the JAK2/STAT3 Signaling Pathway and Mitigation of Hypoxia within the Tumor Microenvironment.

SCOPE: The optimization of anti-cancer drug effectiveness through dietary modifications has garnered significant attention among researchers in recent times. Astaxanthin (AST) has been identified as a safe and biologically active dietary supplement. METHODS AND RESULTS: The tumor-bearing mice are treated with sorafenib, along with supplementation of 60 mg kg-1 AST during the treatment. The coadministration of AST and a subclinical dosage of 10 mg kg-1 sorafenib demonstrates a tumor inhibition rate of 76.5%, which is notably superior to the 45% inhibition rate observed with the clinical dosage of 30 mg kg-1 sorafenib (p < 0.05). The administration of AST leads to a tumor inhibition increase of around 25% when combined with the clinical dose of 30 mg kg-1 sorafenib (p <0.05). AST enhances the inhibitory effect of sorafenib on tumor angiogenesis through the JAK2/STAT3 signaling pathway. Furthermore, AST exhibits a reduction in hypoxia within the tumor microenvironment. CONCLUSION: The results suggest that AST supplement enhances the inhibitory effects of sorafenib on hepatocellular carcinoma. This study presents a new dietary management program for oncology patients.

The Protective and Immunomodulatory Effects of Fucoidan Against 7,12-Dimethyl benz[a]anthracene-Induced Experimental Mammary Carcinogenesis Through the PD1/PDL1 Signaling Pathway in Rats.

Fucoidan is a sulfated polysaccharide that is extracted from brown algae seaweed. This study was designed to evaluate the protective and immunomodulatory effects of dietary fucoidan on 7,12-dimethyl benz[a]anthracene (DMBA)-induced experimental mammary carcinogenesis in rats. Sixty Sprague-Dawley rats were randomly assigned to four equal groups: the control group (control group), the cancer model group (model group), and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg/kg·body weight, respectively. We found that fucoidan treatment decreased the tumor incidence and mean tumor weight and prolonged the tumor latency. Flow cytometric analyses revealed that the number of blood natural killer cells was higher after fucoidan treatment and that the proportions of CD4 and CD8 T cells were also increased. The serum levels of interleukin (IL)-6, IL-12p40, and interferon (IFN)-γ were higher in the rats treated with fucoidan compared to those of model rats. Moreover, the percentage of CD3+ Foxp3+ regulatory T cells in the blood and the levels of IL-10 and transforming growth factor ß in the serum were lower in the rats treated with fucoidan. Furthermore, fucoidan treatment decreased the expression of Foxp3 and programmed cell death 1 ligand 1 (PDL1) in tumor tissues. The levels of p-phosphatidyl inositol kinase 3 and p-AKT in tumor tissues were also lower than those of model rats. These results suggest that a fucoidan-supplemented diet can inhibit DMBA-induced tumors in rats. This study provides experimental evidence toward elucidating the immune enhancement induced by fucoidan through the programmed cell death 1/PDL1 signaling pathway. The immunomodulatory effect is one of the possible mechanisms of the protective effect of fucoidan against mammary carcinogenesis.