Potential use of compounds from sea cucumbers as MDM2 and CXCR4 inhibitors to control cancer cell growth

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Teresa Liliana Wargasetia, Sofy Permana, Nashi Widodo

2018 Experimental and Therapeutic Medicine Vol. 16 Issue 4 Article Cited by 11 Quartile

Abstract

Ineffectiveness of cancer therapy may originate in the incompatibility of the treatment with various mutations in the cancer cells. Finding novel anticancer treatments that work efficiently for varying types of cancer cells remains challenging. Previous studies have identified that compounds in sea cucumbers are capable of inhibiting the growth of cancer cells and inducing apoptosis. However, information on the underlying mechanisms controlling cancer cell growth at a molecular level remains limited. The current study analyzed the potential of colochiroside A, ds-echinoside A, philinopside E, sphingosine and stichoposide C as inhibitors for anticancer target proteins, including mouse double minute 2 homolog (MDM2) and C-X-C chemokine receptor type 4 (CXCR4). Inhibition of MDM2 triggers apoptosis through regulation of tumor protein 53 and CXCR4 inhibition may prevent cancer cell proliferation and growth by affecting the Janus kinase 2/3 signal transducer and activator of transcription signaling pathway and protein tyrosine kinase 2. The results of a binding affinity analysis using molecular docking revealed that philinopside E and ds-echinoside A may inhibit MDM2 and CXCR4. The data suggested that these active compounds may be promising inhibitors of cell growth by binding to two targets simultaneously. Furthermore, stichoposide C and colochiroside A were predicted to inhibit CXCR4. Additional research is needed to validate the in vitro activity of the aforementioned compounds. © 2018, Spandidos Publications. All rights reserved.

Affiliations

Faculty of Medicine, Maranatha Christian University, Bandung, 40164, West Java, Indonesia; Biology Department, Faculty of Mathematics and Natural Sciences, The University of Brawijaya, Malang, 65145, East Java, Indonesia