Fucoxanthin Inhibits Development of Sigmoid Colorectal Cancer in a PDX Model With Alterations of Growth, Adhesion,
Masaru Terasaki1,2, Kirara Tsuruoka3, Takuji Tanaka4
1School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan; terasaki@hoku-iryo-u.ac.jp.
Background/Aim:
Fucoxanthin (Fx), a dietary marine xanthophyll, exerts potent anticancer effects in various colorectal cancer (CRC) animal models. However, therapeutic effects of Fx in human cancer tissues remain unclear. A patient-derived xenograft (PDX) mouse model transplanted with cancer tissues from patients is widely accepted as the best preclinical model for evaluating the anticancer potential of drug candidates.
Materials And Methods:
Herein, we investigated the anticancer effects of Fx in PDX mice transplanted with cancer tissues derived from a patient with CRC (CRC-PDX) using LC-MS/MS- and western blot-based proteome analysis.
Results:
The tumor in the patient with CRC was a primary adenocarcinoma (T3N0M0, stage II) showing mutations of certain genes that were tumor protein p53 (TP53), AT-rich interaction domain 1A (ARID1A), neuroblastoma RAS viral oncogene homolog (NRAS), and PMS1 homolog 2 (PMS2). Administration of Fx significantly suppressed the tumor growth (0.6-fold) and tended to induce differentiation in CRC-PDX mice. Fx up-regulated glycanated-decorin (Gc-DCN) expression, and down-regulated Kinetochore-associated protein DSN1 homolog (DSN1), phospho(p) focal adhesion kinase (pFAK)(Tyr397), pPaxillin(Tyr31), and c-MYC involved in growth, adhesion, and/or cell cycle, in the tumors of CRC-PDX mice than in control mice. Alterations in the five proteins were consistent with those in human CRC HT-29 and HCT116 cells treated with fucoxanthinol (FxOH, a major metabolite of Fx).
Conclusion:
Fx suppresses development of human-like CRC tissues, especially through growth, adhesion, and cell cycle signals.
Insights
Fucoxanthin (Fx) significantly suppressed colorectal cancer (CRC) tumor growth in a patient-derived xenograft model. This marine compound impacts key proteins involved in cancer cell growth, adhesion, and cell cycle regulation.
Area of Science:
- Marine natural products
- Cancer biology
- Proteomics
Background:
- Fucoxanthin (Fx), a marine xanthophyll, shows anticancer potential in preclinical models.
- Its efficacy in human colorectal cancer (CRC) tissues requires further investigation.
- Patient-derived xenograft (PDX) models offer a robust platform for evaluating drug candidates in human-like cancer environments.
Purpose of the Study:
- To investigate the anticancer effects of Fx on human colorectal cancer (CRC) tissues.
- To analyze the molecular mechanisms underlying Fx's therapeutic potential using proteomic analysis.
- To evaluate Fx in a patient-derived xenograft (PDX) mouse model.
Main Methods:
- Utilized a patient-derived xenograft (PDX) mouse model engrafted with human colorectal cancer (CRC) tissue.
- Administered Fx to CRC-PDX mice and assessed tumor growth and differentiation.
- Employed LC-MS/MS and western blot-based proteome analysis to identify molecular changes in tumors.
Main Results:
- Fx administration significantly suppressed tumor growth (0.6-fold) and promoted differentiation in CRC-PDX mice.
- Fx modulated the expression of key proteins: up-regulating glycanated-decorin (Gc-DCN) and down-regulating DSN1, pFAK, pPaxillin, and c-MYC.
- Observed protein alterations were consistent with those in human CRC cell lines treated with fucoxanthinol (FxOH), Fx's major metabolite.
Conclusions:
- Fucoxanthin (Fx) demonstrates efficacy in suppressing the development of human-like colorectal cancer (CRC) tissues.
- Fx exerts its effects by targeting molecular pathways involved in cancer cell growth, adhesion, and cell cycle regulation.
- These findings support the potential of Fx as a therapeutic agent for colorectal cancer.
