Fucoxanthin administration delays occurrence of tumors in xenograft mice by colonospheres, with an anti-tumor predictor of glycine

Abstract

Fucoxanthin and its major metabolite, fucoxanthinol, have potent anti-cancer properties in carcinogenic model mice and against cancer cells. Evidence has accumulated regarding the diagnostic potential of biological metabolites as invasive and non-invasive obtainable approaches. We recently demonstrated that glycine was an effective predictor of the suppression of sphere formation and epithelial mesenchymal transition by fucoxanthinol in human colorectal cancer stem-like spheroids (colonospheres) under normoxia and hypoxia. In the present study, we investigated the suppressive effect of fucoxanthin on tumorigenesis derived from colonospheres in xenograft mice, and the alteration on the metabolite profiles of mouse tumors by fucoxanthin was evaluated. Fucoxanthin administration at 2.5 mg/kg body weight (p.o.) for 4 weeks significantly inhibited the incidence of tumors by inoculation of colonospheres suspension in BALB/c nu/nu mice compared with control mice, but not tumor sizes. In addition, fucoxanthin down-regulated tumor Cyclin D1 expression by 0.7-fold of that observed in the tumors of the control mice. Moreover, the tumor glycine level in the xenograft mice was decreased by fucoxanthin administration to 0.5-fold. These results imply the possibility of tumor metabolites as a prediction marker of tumorigenicity derived from colorectal cancer stem cells in mice.

Nutraceutical characteristics of the brown seaweed carotenoid fucoxanthin

“…In addition, Fx induced anchorage-dependent apoptosis in human colorectal cancer (CRC) cells through the suppression of integrin signals [129,130]. In animal models, Fx administration significantly suppressed tumor development in a xenograft model of colorectal cancer [127,131], decreased the number of colorectal polyps, and decreased colonic lesions compared to untreated control mice [132]. In addition, Fx administration resulted in significantly lower numbers of colorectal cancer stem cell-like cells, cancer-associated fibroblast-like, tumor-associated macrophage-like and dendritic cell-like cells in colonic mucosa compared to untreated control mice [132].…”

SOX9 is associated with advanced T-stages of clinical stage II colon cancer in young Mexican patients

“…According to Bahmad et al , these studies primarily relied on two main criteria in their assessment: average volume of the generated spheres (size) and the average number of sphere-forming units (SFU) ( 52 ). Although our study did not evaluate SFU, size of colonosphere represents the proliferation of cells in the tumor mass, the capability of adhesion, and the anoikis resistance (AR) ( 53 , 54 ). A study demonstrated that SOX9 silencing resulted in AR loss in HCT116 cells.…”

Fucoxanthin and Colorectal Cancer Prevention

“…Consequently, we have revealed that the administration of Fx and FxOH inhibited tumorigenesis in xenograft NOD/SCID and BALB/c mice, respectively, subcutaneously injected with CCSCs-like cells prepared from human CRC HT-29 cells. In addition, the administration of Fx to BALB/c mice significantly downregulated the cyclin D1 expression in the tumor [ 97 , 116 ]. Furthermore, we investigated the effect of Fx in a Apc Min/+ mouse model of human FAP.…”