Determination of Potential Molecular Targets of Butein Colorectal Cancer Treatment via In-Silico Analyses

Year 2026, Volume: 2 Issue: 1, 28 - 42, 30.01.2026

Sevda Sağ Bayav , İbrahim Bayav , Ekrem Darendelioğlu

Abstract

Introduction: Colorectal cancer remains one of the most challenging malignancies due to its high incidence, molecular
heterogeneity, and rapid development of resistance to therapy. The limitations of single-target treatments highlight the need for
multi-target agents capable of simultaneously suppressing key oncogenic networks. This study aimed to comprehensively investigate
the therapeutic potential of butein, a natural chalcone, in CRC using multi-step in silico bioinformatics approaches. Materials and
Methods: To evaluate the molecular mechanisms and clinical significance of butein in CRC, several complementary analyses were
performed. Network-based bioinformatic, protein-protein interaction, and functional enrichment analyses were used to explore
molecular pathways. Expression analyses were conducted using transcriptomic and proteomic datasets. Promoter methylation and
survival analyses were performed to assess epigenetic regulation and clinical relevance. Finally, molecular docking studies were
carried out for structural validation. Results: PTGS2, TERT, and EGFR were identified as common targets of butein and CRC.
HSP90AA1, ERBB2, IL6, TP53, and EGFR were identified as center genes. Enrichment analyses revealed significant clustering in
the ErbB, MAPK, PI3K and AKT, signaling pathways. Expression and survival analyses demonstrated that altered expression of hub
genes was significantly associated with CRC progression and patient outcomes. Molecular docking analyses showed that butein
binds effectively to all hub proteins, particularly ERBB2 and HSP90AA1, through non-covalent interactions, supporting its multitarget
inhibitory potential. Conclusion: This study demonstrates that butein exerts a rational multi-target therapeutic effect in CRC
by concurrently targeting ErbB signaling and its key regulator HSP90AA1. These findings support butein as a promising therapeutic
candidate, warranting further experimental validation.

Keywords

Butein , Colorectal cancer , ERBB signaling pathway , HSP90AA1

References

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