Cryptotanshinone Is a Intervention for ER-Positive Breast Cancer: An Integrated Approach to the Study of Natural Product Intervention Mechanisms

Abstract

Background: Resistance to endocrine therapy has hampered clinical treatment in patients with ER-positive breast cancer (BRCA). Studies have confirmed that cryptotanshinone (CPT) has cytotoxic effects on BRCA cells and can significantly inhibit the proliferation and metastasis of ER-positive cancer cells.Methods: We analyzed the gene high-throughput data of ER-positive and negative BRCA to screen out key gene targets for ER-positive BRCA. Finally, the effects of CPT on BRCA cells (MCF-7 and MDA-MB-231) were examined, and quantitative RT-PCR was used to evaluate the expression of the key targets during CPT intervention.Results: A total of 169 differentially expressed genes were identified, and revealed that CPT affects the ER-positive BRCA cells by regulating CDK1, CCNA2, and ESR1. The overall experimental results initially show that MCF-7 cells were more sensitive to CPT than MDA-MB-231 cells, and the expression of ESR1 was not affected in the BRCA cells during CPT intervention, while the expression of CDK1 and CCNA2 were significantly down-regulated.Conclusion: CPT can inhibit the proliferation and migration of BRCA cells by regulating CDK1, CCNA2, and ESR1, especially in ER-positive BRCA samples. On the one hand, our research has discovered the possible mechanism that CPT can better interfere with ER+ BRCA; on the other hand, the combination of high-throughput data analysis and network pharmacology provides valuable information for identifying the mechanism of drug intervention in the disease.

Interpreting the Pharmacological Mechanisms of Sho-saiko-to on Thyroid Carcinoma through Combining Network Pharmacology and Experimental Evaluation

“…Molecular docking is a kind of computer technology that could reveal the relationship between the chemical components and the target proteins in the treatment of diseases. 48 Therefore, the molecular docking was used to clarify the chemical ingredients of Sho-saiko-to and related targets against TC, which could explain the action mechanism and binding affinity of target proteins and active components to some extent. First, the compound structure in the Pubchem platform (https:// pubchem.ncbi.nlm.nih.gov/) was downloaded and transformed to mol2 format file through Chem 3D software and then was downloaded the crystal structure of protein targets (PI3KCG, AKT1, CASPASE3, TP53, MYC, STAT3) from RCSB platform (https://www.rcsb.org/).…”

“…Molecular docking is a kind of computer technology that could reveal the relationship between the chemical components and the target proteins in the treatment of diseases . Therefore, the molecular docking was used to clarify the chemical ingredients of Sho-saiko-to and related targets against TC, which could explain the action mechanism and binding affinity of target proteins and active components to some extent.…”