Curcumin and its Analogue Targeting β-Catenin and GSK-3β in Wnt Signaling Pathways: In Vitro and In Silico Study Murwanti Retno1,*, Kholifah Eva2, Sudarmanto B. S. Ari3, Hermawan Adam3 1Department of Pharmacology and Clinic, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, D. I. Yogyakarta, 55281, Indonesia 2Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta-55281 3Departement of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, D. I. Yogyakarta, 55281, Indonesia *Corresponding Author E-mail: retno_murwanti@ugm.ac.id
Online published on 30 April, 2020. Abstract Curcumin, the yellow pigment isolated from turmeric has been reported to suppress migration through inhibition of β-catenin and GSK-3β, which is activated in metastasis breast cancer. However, the effects of its analog pentagamavunon-1 (PGV-1) on the Wnt/β-catenin pathway have not been investigated. This present study aims to determine the effect of curcumin and its analog to inhibition of breast cancer cell migration. Step of procedure was cultured 4T1 cell and simulation in silico study. This study showed that PGV-1 suppressed migration of 4T1 breast cancer cell. Besides, molecular docking study revealed that curcumin showed interaction with Asn516 and PGV-1 interact with His470, Asn430, and Lys435 of β-catenin active site. Moreover, curcumin interacts with GSK-3β at Phe67, Asp 90 and Glu97 while PGV-1 interact at Asp200. Thus, our findings suggest that curcumin and PGV-1 inhibit migration of 4T1 breast cancer by modulating the interaction with β-catenin and GSK-3β. Top Keywords Curcumin, PGV-1, anti-migration, β-catenin, GSK-3β. Top |