A synthetic benzoxazine dimer derivative targets c-Myc to inhibit colorectal cancer progression

Sriratanasak N, Nutho B, Wattanathana W, Phaonakrop N, Panasawatwong B, Erlenbach-Wünsch K, Roytrakul S, Schneider-Stock R, Chanvorachote P (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Molecular Oncology Wiley

DOI: 10.1002/1878-0261.70127

Abstract

The c-Myc protein is a well-known oncoprotein that plays a crucial role in regulating cell growth, proliferation, and differentiation. The overexpression or dysregulation of c-Myc is commonly associated with tumorigenesis in several cancers, including colorectal cancer (CRC). c-Myc forms a heterodimer with its partner MAX to activate the expression of various genes. Here, we synthesized a novel c-Myc-targeting small molecule, 2,2′-((cyclohexylazanedyl)bis(methylene))bis(4-ethylphenol), or ECD, and demonstrate ECD's anticancer activity via interference with the c-Myc/MAX dimer to promote c-Myc degradation in CRC cells in vitro, in silico, and in vivo. This study revealed the activity of ECD toward CRC cells as a c-Myc inhibitor. Computer-aided analysis revealed that the effect of ECD was mediated through disturbance of the c-Myc/MAX complex. Moreover, ECD exhibited cytotoxic activity by inducing DNA damage, leading to apoptotic cell death. This DNA damage-inducing property was also confirmed by whole-proteome profiling of HT29 cells after ECD treatment. In the chick embryo chorioallantoic membrane (CAM) xenograft assay, we demonstrated a remarkable inhibition of the tumorigenic activity upon ECD exposure. In summary, we identified ECD as a novel potent compound targeting the oncoprotein c-Myc that may offer new opportunities for CRC treatment.

Authors with CRIS profile

Katharina Erlenbach-Wünsch Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Regine Schneider-Stock Professur für Experimentelle Tumorpathologie

Involved external institutions

Chulalongkorn University / จุฬาลงกรณ์มหาวิทยาลัย TH Thailand (TH) Mahidol University / มหาวิทยาลัยมหิดล TH Thailand (TH) Kasetsart University / มหาวิทยาลัยเกษตรศาสตร์ TH Thailand (TH) National Center for Genetic Engineering and Biotechnology TH Thailand (TH)

How to cite

APA:

Sriratanasak, N., Nutho, B., Wattanathana, W., Phaonakrop, N., Panasawatwong, B., Erlenbach-Wünsch, K.,... Chanvorachote, P. (2025). A synthetic benzoxazine dimer derivative targets c-Myc to inhibit colorectal cancer progression. Molecular Oncology. https://doi.org/10.1002/1878-0261.70127

MLA:

Sriratanasak, Nicharat, et al. "A synthetic benzoxazine dimer derivative targets c-Myc to inhibit colorectal cancer progression." Molecular Oncology (2025).

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