astaxanthine and Neoplasm-Metastasis

Breast cancer (BC) is a major public health problem diagnosed in more than 2 million women worldwide in 2018, causing more than 600,000 deaths. 90% of deaths due to breast cancer are caused by metastasis. Metastasis is a complex process that is divided into several steps, including separation of tumor cells from the primary tumor, invasion, cell migration, intravasation, vasculature survival, extravasation, and colonization of the secondary site. Astaxanthin (AXT) is a marine-based ketocarotenoid that has many different potential functions such as anti-oxidant, anti-inflammatory and oxidative stress-reducing properties to potentially reduce the incidence of cancer or inhibit the expansion of tumor cells. This study aims to investigate the effects of astaxanthin as a new metastasis inhibitor on T47D human invasive ductal carcinoma breast cancer cell.. To investigate the effects of the astaxanthin as a new metastasis inhibitor on T47D cell, expression levels of anti-maspin, anti-Kai1, anti-BRMS1, and anti-MKK4 were examined by western blot. Also, we evaluated differences of these suppressors expression levels in tissue sections of 10 patients diagnosed with in situ and invasive ductal carcinoma by immunohistochemistry method.. 250 μM astaxanthin increased the activation of all metastasis suppressing proteins. Also, these metastasis suppressors showed higher expression in invasive ductal carcinoma tissues than in situ ductal carcinoma patients.. We think that astaxanthin is a promising therapeutic agent for invasive ductal carcinoma patients. The effects of astaxanthin on metastasis in breast cancer should be investigated further based on these results.. Breast, cancer, metastasis.. Il cancro al seno (BC) è un grave problema di salute pubblica diagnosticato in oltre 2 milioni di donne in tutto il mondo nel 2018, e che causa oltre 600.000 decessi. Il 90% dei decessi seno sono causati da metastasi, processo complesso suddiviso in diversi passaggi, tra cui la separazione delle cellule tumorali dal tumore primario, l’invasione, la migrazione cellulare, la invasione e la sopravvivenza intravascolare, l’emigrazione extravascolare e la colonizzazione secondaria. L’astaxantina (AXT) è un chetocarotenoide di origine marina che ha molte diverse potenziali funzioni in termini di proprietà antiossidanti, antinfiammatorie e di riduzione dello stress ossidativo in grado di ridurre potenzialmente l’incidenza del cancro o inibire l’espansione delle cellule tumorali. Questo studio mira a indagare gli effetti dell’astaxantina come nuovo inibitore della metastasi sulle cellule di carcinoma mammario invasivo umano di carcinoma duttale T47D. Per studiare gli effetti dell’astaxantina come nuovo inibitore della metastasi sulla cellula T47D, sono stati esaminati mediante western blot i livelli di espressione di anti-maspin, anti-Kai1, anti-BRMS1 e anti-MKK4. Inoltre, abbiamo valutato le differenze dei livelli di espressione di questi soppressori in sezioni di tessuto di 10 pazienti con diagnosi di carcinoma duttale in situ e invasivo con immunoistochimica. Risultato: 250 μM di astaxantina hanno aumentato l’attivazione di tutte le proteine™ che sopprimono le metastasi. Inoltre, questi soppressori di metastasi hanno mostrato una maggiore espressione nei tessuti di carcinoma duttale invasivo rispetto ai pazienti con carcinoma duttale in situ. In conclusione riteniamo che l’astaxantina sia un promettente agente terapeutico per le pazienti con carcinoma duttale invasivo. Gli effetti dell’astaxantina sulle metastasi nel cancro al seno dovrebbero essere ulteriormente studiati sulla base di questi risultati.

Topics: Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Neoplasm Metastasis; Xanthophylls

3S, 3'S-Astaxanthin is the most powerful antioxidant to scavenge free radicals in the world. In this study, a 3S, 3'S-astaxanthin biosynthesis pathway was constructed in a probiotic yeast, Kluveromyces marxianus, denoted YEAST, and its bioactive metabolites were extracted for biofunctional assessments. The bio-safety examination was achieved by two animal models as following: First, no significant toxic effects on YEAST groups were found in zebrafish; Second, after feeding YEAST for 4 weeks, the rat-groups showed no visible abnormality, and no significant change of the body weight and blood biochemistry tests. The inhibition of lung metastasis of melanoma cells and the increment of the survival rate were demonstrated by feeding YEAST and injecting the intravenous commercial astaxanthin in vivo rodent model. Based on in vitro assays of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) scavenging analysis, ferrous ion chelating ability, reducing power assessment, and mushroom tyrosinase inhibition evaluation, YEAST-astaxanthin showed anti-oxidative and tyrosinase suppressive properties. Taken together, the 3S, 3'S-astaxanthin producing probiotic yeast is safe to be used in the bio-synthesis of functional and pharmaceutical compounds, which have broad industrial applications on cosmetic, food and feed additive and healthcare.

Topics: Animals; Antioxidants; Female; Kluyveromyces; Male; Melanoma, Experimental; Metabolic Engineering; Mice; Mice, Inbred BALB C; Monophenol Monooxygenase; Neoplasm Metastasis; Probiotics; Rats; Rats, Sprague-Dawley; Xanthophylls; Zebrafish

We investigated the effects of astaxanthin on the antitumor effector activity of natural killer (NK) cells suppressed by stress in mice in order to define the immunological significance of astaxanthin (ASX) when combined with restraint stress treatment. When the mice were treated with restraint stress alone, the total number of spleen cells, and the level NK cell activity per spleen were reduced to a nadir on day 3. The stress also caused a significant increase in the lipid peroxidation of liver tissue. ASX (100 mg/kg/day, p.o., 4 days) improved the immunological dysfunction induced by restraint stress. On the other hand, metastatic nodules were observed in the livers of syngenic DBA/2 mice on day 12 after inoculation of P815 mastocytoma cells. Hepatic metastasis was promoted further by restraint stress when applied on day 3 before the inoculation of P815. Daily oral administration of ASX (1 mg/kg/day, p.o., 14 days) markedly attenuated the promotion of hepatic metastasis induced by restraint stress. These results suggested that astaxanthin improves antitumor immune responses by inhibiting of lipid peroxidation induced by stress.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antioxidants; beta Carotene; Cells, Cultured; Female; Immunosuppressive Agents; Killer Cells, Natural; Lipid Peroxidation; Liver; Liver Neoplasms; Mast-Cell Sarcoma; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasm Metastasis; Neoplasm Transplantation; Restraint, Physical; Stress, Psychological; Thiobarbituric Acid Reactive Substances; Tissue Distribution; Tumor Cells, Cultured; Xanthophylls