Nudibranch Bioactive Compounds for Anti-Breast Cancer Therapy: A Review and In Silico Studies Targeting ERα and NUDT5

Marine mollusks, particularly nudibranchs, represent an untapped reservoir of bioactive compounds with significant potential for anti-breast cancer activity. This review consolidates and analyzes the morphology of nudibranchs, their bioactive metabolites, and the molecular mechanisms underlying their Anti-cancer effects. Additionally, it explores the in-silico interactions of nudibranch-derived compounds with two key targets in hormone receptor-positive breast cancer: estrogen receptor alpha (ERα) and nucleoside diphosphate-linked moiety X-type motif 5 (NUDT5). Molecular docking simulations identified ulapualide A as the most promising candidate, exhibiting strong binding affinities and stable interactions with both ERα and NUDT5, surpassing other bioactive compounds. The proposed dual-targeting mechanism of ulapualide A involves competitive inhibition of ERα by blocking estrogen binding, preventing receptor dimerization and nuclear translocation, thereby reducing the transcription of pro-cancer genes. Simultaneously, ulapualide A inhibits NUDT5 activity, which is essential for disrupting nuclear ATP production and depleting the energy supply required for ERα-driven transcription. Thus, this dual inhibition strategy represents a synergetic approach to suppressing breast cancer cell proliferation. Although the in-silico results are promising, additional in-vitro and in-vivo studies are essential to validate the therapeutic efficacy and safety of ulapualide A. This study underscores the potential of marine-derived compounds, particularly nudibranch metabolites, as promising candidates for targeted breast cancer therapy development and as a new avenue for oncology discovery.