Combining In Vitro, In Vivo, and Network Pharmacology Assays to Identify Targets and Molecular Mechanisms of Spirulina-Derived Biomolecules against Breast Cancer

What is it about?

The current study unequivocally establishes that Spirulina (SP) extract acts as a chemopreventive agent against breast cancer, attributing its efficacy to limit cell proliferation, induce apoptosis, antiestrogenic effects, and antioxidant properties. The validation of these effects was conducted in an MCF-7 cell line, representing human breast adenocarcinomas expressing the estrogen receptor. Through comprehensive phytoconstituent profiling, network-based pharmacology, and molecular docking analyses, key therapeutic component and their targets for breast cancer were accurately identified. Central to this investigation are key compounds including 7- hydroxycoumarin derivatives of cinnamic acid, hinokinin, valeric acid, and α-linolenic acid. Three important proteins—EGFR, PI3K-AKT, and ERK1/2 MAPK—are the specific targets of these substances. The findings suggest that SP constituents induce apoptosis and impede cell proliferation by inhibiting the EGFR/Akt and ERK1/2 MAPK signaling pathways. Moving forward, the development of small-molecule inhibitors targeting the EGFR/Akt and ERK1/2 MAPK pathways for BC prevention and therapy requires a rigorous validation of active components and their corresponding targets.

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Photo by National Cancer Institute on Unsplash

Photo by National Cancer Institute on Unsplash

Why is it important?

The findings revealed that administering 1 g/kg of SP increased antioxidant activity by elevating levels of catalase (CAT) and superoxide dismutase (SOD), while reducing levels of malonaldehyde (MDA) and protein carbonyl. Histological examination demonstrated a decrease in tumor occurrence, reduced estrogen receptor expression, suppressed cell proliferation, and promoted apoptosis in SP-treated animals. Furthermore, SP disrupted the G2/M phase of the MCF-7 cell cycle, inducing apoptosis and reactive oxygen species (ROS) accumulation. SP also enhanced intrinsic apoptosis in MCF-7 cells by upregulating cytochrome c, Bax, caspase-8, caspase-9, and caspase-7 proteins, while downregulating Bcl-2 production. The main compounds identified in the LC-MS/MS study of SP included 7-hydroxycoumarin derivatives of cinnamic acid, hinokinin, valeric acid, and α-linolenic acid. These substances specifically targeted three crucial proteins: ERK1/2 MAPK, PI3K-protein kinase B (AKT), and the epidermal growth factor receptor (EGFR). Network analysis and molecular docking indicated a significant binding affinity between SP and these proteins, which was confirmed by Western blot analysis showing decreased protein levels of p-EGFR, p-ERK1/2, and p-AKT following SP administration. Ultimately, SP was reported to suppress MCF-7 cell growth and induce apoptosis by modulating the PI3K/AKT/EGFR and MAPK pathways.

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