The Synergistic Mechanism of Chelidonium majus Alkaloids on Melanoma Treatment via a Multi-Strategy Insight

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Abstract
Melanoma represents a formidable challenge in dermatological oncology due to its resistance to conventional treatments. The Celandine Alkali Injection Formula (CAIF) offers benefits on clinical internal medicine treatments, within which chelidonine and tetrandrine are recognized as potential quality markers. However, their synergistic mechanisms facilitating their anti-melanoma action remain unveiled. This study embarked on an exploration of CAIF’s therapeutic potential through a multifaceted research design, integrating system pharmacological predictions with empirical molecular biological evaluations. The dual application of chelidonine and tetrandrine within CAIF exhibited a pronounced inhibitory effect on the proliferation of B16F10 cells, surpassing the effectiveness of individual compound administration. Computational predictions identified the top 50 targets, involved in key signaling pathways including cell cycle regulation, and melanogenesis. RNA sequencing further elucidated that the combinatory treatment modulated a broader spectrum of differentially expressed genes, implicating crucial biological processes including cell differentiation, and tyrosinase metabolism. The combination markedly enhanced melanogenesis and apoptotic indices, arrested cell cycle progression, and fostered cellular differentiation. Notably, chelidonine additionally curtailed the migratory capacity of B16F10 cells. Our findings underscore the therapeutic potential of chelidonine and tetrandrine, key components of CAIF, in effectively combating melanoma by targeting cell proliferation, migration, differentiation, and melanogenesis.
Funding Information
  • National Natural Science Foundation of China (U1603122, 22207012, 1811)
  • Tianfu Emei Creative & Leading Talents of Sichuan province (U1603122, 22207012, 1811)

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