Tumor suppression by resistant maltodextrin, Fibersol-2

Abstract

Resistant maltodextrin Fibersol-2 is a soluble and fermentable dietary fiber that is Generally Recognized As Safe (GRAS) in the United States. We tested whether Fibersol-2 contains anti-tumor activity. Human colorectal cancer cell line, HCT116, and its isogenic cells were treated with FIbersol-2. Tumor growth and tumorigenesis were studied in vitro and in vivo. Apoptotic pathway and generation of reactive oxygen species (ROS) were investigated. We discovered that Fibersol-2 significantly inhibits tumor growth of HCT116 cells by inducing apoptosis. Fibersol-2 strongly induces mitochondrial ROS and Bax-dependent cleavage of caspase 3 and 9, which is shown by isogenic HCT116 variants. Fibersol-2 induces phosphorylation of Akt, mTOR in parental HCT116 cells, but not in HCT116 deficient for Bax or p53. It prevents growth of tumor xenograft without any apparent signs of toxicity in vivo. These results identify Fibersol-2 as a mechanism-based dietary supplement agent that could prevent colorectal cancer development.

Keywords:

• apoptosis
• colorectal cancer
• Fibersol-2
• p53
• resistant maltodextrin
• reactive oxygen species

Acknowledgment

We thank all the members of the Ouchi Laboratory for helpful discussion. We particularly thank Dr. Bert Vogelstein at Johns Hopkins University for providing us with isogenic HCT116 cell lines.

Funding

This work is supported by Matsutani America Cancer Research Fund, R01CA79892, R01CA90631, and 5P30CA16056 from National Institutes of Health, and Breast Cancer Research Grant from Susan G. Komen Foundation.

Author Contributions

E.Y.S., M.O., S.C.S., S.L.O. and T.O. planned and generated all the data. E.Y.S, D.R., K.S., and T.O. discussed the results, and E.Y.S. and T.O. wrote the paper.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.