Combining In Vitro, In Vivo, and Network Pharmacology Assays to Identify Targets and Molecular Mechanisms of Spirulina-Derived Biomolecules against Breast Cancer.
Soha Osama Mahmoud HassaninAmany Mohammed Mohmmed HegabReham Hassan MekkyMohamed Adel SaidMona G KhalilAlaaeldin Ahmed HamzaAmr AminPublished in: Marine drugs (2024)
The current research employed an animal model of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland carcinogenesis. The estrogen receptor-positive human breast adenocarcinoma cell line (MCF-7) was used for in vitro analysis. This was combined with a network pharmacology-based approach to assess the anticancer properties of Spirulina (SP) extract and understand its molecular mechanisms. The results showed that the administration of 1 g/kg of SP increased the antioxidant activity by raising levels of catalase (CAT) and superoxide dismutase (SOD), while decreasing the levels of malonaldehyde (MDA) and protein carbonyl. A histological examination revealed reduced tumor occurrence, decreased estrogen receptor expression, suppressed cell proliferation, and promoted apoptosis in SP protected animals. In addition, SP disrupted the G2/M phase of the MCF-7 cell cycle, inducing apoptosis and reactive oxygen species (ROS) accumulation. It 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 were 7-hydroxycoumarin derivatives of cinnamic acid, hinokinin, valeric acid, and α-linolenic acid. These substances specifically targeted three important 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. This was verified by Western blot analysis that revealed decreased protein levels of p-EGFR, p-ERK1/2, and p-AKT following SP administration. SP was finally reported to suppress MCF-7 cell growth and induce apoptosis by modulating the PI3K/AKT/EGFR and MAPK signaling pathways suggesting EGFR as a potential target of SP in breast cancer (BC) treatment.
Keyphrases
- signaling pathway
- epidermal growth factor receptor
- cell cycle arrest
- induced apoptosis
- cell proliferation
- pi k akt
- cell death
- oxidative stress
- endoplasmic reticulum stress
- cell cycle
- small cell lung cancer
- tyrosine kinase
- breast cancer cells
- estrogen receptor
- molecular docking
- reactive oxygen species
- network analysis
- advanced non small cell lung cancer
- protein kinase
- endothelial cells
- south africa
- mass spectrometry
- protein protein
- high throughput
- high glucose
- radiation therapy
- hydrogen peroxide
- molecular dynamics simulations
- smoking cessation
- capillary electrophoresis
- amino acid