Mechanism of Procyanidin B2 in the Treatment of Chronic Myeloid Leukemia Based on Integrating Network Pharmacology and Molecular Docking.

OBJECTIVE: To study the pharmacological mechanism of procyanidin B2 (PCB2) on chronic myeloid leukemia (CML) by integrating network pharmacological methods systematically. METHODS: Firstly, the potential target genes of PCB2 were predicted by the pharmacological database and analysis platform (TCMSP and Pharmmapper). Meanwhile, the relevant target genes of CML were collected from GeneCards and DisGene. Pooled data were collected to screen for common target genes. Furthermore, the above intersection genes were imported into the String website to construct a protein-protein interaction (PPI) network, and the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were further analyzed. Besides, molecular docking was performed to verify the possible binding conformation between PCB2 and candidate targets. Finally, MTT and RT-PCR experiments of K562 cells were performed to verify the above results of network pharmacology. RESULTS: A total of 229 PCB2 target genes were retrieved, among which 186 target genes had interaction with CML. The pharmacological effects of PCB2 on CML were related to some important oncogenes and signaling pathways. The top ten core targets predicted by Network Analysis were as follows: AKT1, EGFR, ESR1, CASP3, SRC, VEGFA, HIF1A, ERBB2, MTOR, and IGF1. Molecular docking studies confirmed that hydrogen bonding was the main interaction force of PCB2 binding targets. According to the molecular docking score, the following three target proteins were most likely to bind to PCB2: VEGFA (-5.5 kcal/mol), SRC (-5.1 kcal/mol), and EGFR (-4.6 kcal/mol). After treatment of PCB2 for 24h, mRNA expression levels of VEGFA and HIF1A decreased significantly in K562 cells. CONCLUSION: Through integrating network pharmacology combined with molecular docking, the study revealed the potential mechanism of PCB2 anti-chronic myeloid leukemia.

Mechanism of salidroside in the treatment of chronic myeloid leukemia based on the network pharmacology and molecular docking.

BACKGROUND: Salidroside is a phenolic natural product, which is a kind of Rhodiola rosea. It has been confirmed that it has inhibitory effects on chronic myeloid leukemia, but the specific performance of its molecular effects is still unclear. OBJECTIVE: To systematically study the pharmacological mechanism of salidroside on chronic myeloid leukemia by means of network pharmacology. METHODS: First, the possible target genes of salidroside were predicted through the Traditional Chinese Medicine Pharmacology Database and Analysis Platform, the target gene names were converted into standardized gene names using the Uniprot website. At the same time, the related target genes of chronic myeloid leukemia were collected from GeneCards and DisGenet; Collect summary data and screen for commonly targeted genes. Then, the above-mentioned intersected genes were imported into the String website to construct the protein-protein interaction (PPI) network, and the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were further analyzed. To investigate the overall pharmacological effects of salidroside on chronic myeloid leukemia, we constructed a drug component-target gene-disease (CTD) network. Finally, molecular docking was performed to verify the possible binding conformation between salidroside and the candidate target. RESULTS: A total of 126 salidroside target genes were retrieved, and 106 of them had interactions with chronic myeloid leukemia. The pharmacological effects of salidroside on chronic myeloid leukemia are related to some important oncogenes and signaling pathways. Molecular docking studies confirmed that the main role of salidroside binding to the target genes is hydrogen bonding. CONCLUSIONS: We revealed the potential mechanism of action of salidroside against chronic myeloid leukemia, verified by network pharmacology combined with molecular docking. However, salidroside is a promising drug for the prevention and treatment of chronic myeloid leukemia, and further research is needed to prove it.

Icaritin: A Novel Natural Candidate for Hematological Malignancies Therapy.

Hematological malignancies including leukemia and lymphoma can severely impact human health. With the current therapies combined with chemotherapy, stem cell transplantation, radiotherapy, and immunotherapy, the prognosis of hematologic malignancies improved significantly. However, most hematological malignancies are still incurable. Therefore, research for novel treatment options was continuing with the natural product as one source. Icaritin is a compound extracted from a traditional Chinese herb, Epimedium Genus, and demonstrated an antitumor effect in various neoplasms including hematological malignancies such as leukemia, lymphoma, and multiple myeloma. In hematological malignancies, icaritin showed multiple cytotoxic effects to induce apoptosis, arrest the cell cycle, inhibit proliferation, promote differentiation, restrict metastasis and infiltration, and suppress the oncogenic virus. The proved underlying mechanisms of the cytotoxic effects of icaritin are different in various cell types of hematological malignancies but associated with the critical cell signal pathway, including PI3K/Akt, JAK/STAT3, and MAPK/ERK/JNK. Although the primary target of icaritin is still unspecified, the existing evidence indicates that icaritin is a potential novel therapeutic agent for neoplasms as with hematological malignancies. Here, in the field of hematology, we reviewed the reported activity of icaritin in hematologic malignancies and the underlying mechanisms and recognized icaritin as a candidate for therapy of hematological malignancies.

Effects of AZT and RNA-protein complex (FA-2-b-beta) extracted from Liang Jin mushroom on apoptosis of gastric cancer cells.

AIM: To investigate the synergistic effects of 3'-azido-3'-deoxythymidine (AZT) and FA-2-b-beta extracted from Ling Jin mushroom on apoptosis of gastric cancer cells MKN45 in vitro. METHODS: MTT analysis was made to examine the inhibition rate of MKN45 cells treated with AZT (2.5, 5, 10 and 20 mg/L) and FA-2-b-beta (5, 10, 20 and 40 mg/L) singly and combinatively for 24, 48 and 72 h. Apoptotic effects were evaluated by morphological methods, DNA agarose gel electrophoresis and flow cytometry, respectively. Telomerase activity was estimated by TRAP-ELISA. The mRNA expression of caspase-3 and Bcl-2 were detected by RT-PCR. RESULTS: AZT and FA-2-b-beta could significantly inhibit MKN45 cell proliferation and induce its apoptosis. MKN45 cells were inhibited in dose- and time- dependent manner. The inhibition effect of AZT combined with FA-2-b-beta was obviously better than that used singly (0.469 +/- 0.022 vs 1.075 +/- 0.055, P < 0.05, 0.325 +/- 0.029 vs 0.469 +/- 0.022 P < 0.01). AZT used singly and combination of FA-2-b-beta could decrease the activity of tumor cell telomerase, and AZT has synergistic function with FA-2-b-beta. A certain concentration of AZT could up-regulate the expression of caspase-3 mRNA (r = 0.9969, P < 0.01), which was positively related to apoptosis rate, and could down-regulate the expression of Bcl-2 mRNA, which was negatively related to apoptosis rate (r = 0.926, P < 0.01). Furthermore, the effect of AZT combined with FA-2-b-beta was significantly higher than that used singly. CONCLUSION: Combination of AZT and FA-2-b-beta has an obviously synergetic effect in the gastric cancer cells MKN45, which has provided a new approach to the treatment of gastric cancer clinically.