Curcumin analog GO-Y030 inhibits tumor metastasis and glycolysis

Author:

MaruYama Takashi12ORCID,Miyazaki Hirofumi1,Komori Taishi3,Osana Shion4,Shibata Hiroyuki5,Owada Yuji1,Kobayashi Shuhei1

Affiliation:

1. Tohoku University Graduate School of Medicine Department of Organ Anatomy, , Seiryo 2-1, Aoba, Sendai, Miyagi, 980-8575, Japan

2. Akita University, Graduate School of Medicine Department of Immunology, , Hondo 1-1, Akita, Akita, 010-8543, Japan

3. National Institutes of Health Molecular Biology of Bones and Teeth Section, National Institute of Dental and Craniofacial Research(NIDCR), , 30 convent drive, Building 30, Bethesda, MD, 20892, USA

4. University of Electro-Communications, Graduate School of Informatics and Engineering Department of Engineering Science, , Chofugaoka 1-5-1, Chofu, Tokyo, 182-8585, Japan

5. Akita University, Graduate School of Medicine Department of Clinical Oncology, , Hondo 1-1, Akita, Akita, 010-8543, Japan

Abstract

Abstract Tumor metastasis is one of the worst prognostic features of cancer. Although metastasis is a major cause of cancer-related deaths, an effective treatment has not yet been established. Here, we explore the antitumor effects of GO-Y030, a curcumin analog, via various mechanisms using a mouse model. GO-Y030 treatment of B16-F10 melanoma cells inhibited TGF-β expression and glycolysis. The invasion assay results showed almost complete invasion inhibition following GO-Y030 treatment. Mouse experiments demonstrated that GO-Y030 administration inhibited lung tumor metastasis without affecting vascular endothelial cells. Consistent with this result, GO-Y030 treatment led to the downregulation of MMP2 and VEGFα, inhibiting tumor invasion and metastasis. The silencing of eIF4B, a downstream molecule of S6, attenuated MMP2 expression. Our study demonstrates the novel efficacy of GO-Y030 in inhibiting tumor metastasis by regulating metastasis-associated gene expression via inhibiting dual access, glycolytic and TGF-β pathways.

Funder

Intramural Research Program of NIDCR and a Grant-in-Aid for Scientific Research

Grant-in-Aid for Scientific Research

Mishima Kaiun Memorial Foundation

Publisher

Oxford University Press (OUP)

Subject

Molecular Biology,Biochemistry,General Medicine

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