Breast cancer (BC) is one of the most common malignant tumor, the incidence of which has increased worldwide in recent years. Ginsenosides are the main active components of Panax ginseng C. A. Mey., in vitro and in vivo studies have confirmed that ginsenosides have significant anti-cancer activity, including BC. It is reported that ginsenosides can induce BC cells apoptosis, inhibit BC cells proliferation, migration, invasion, as well as autophagy and angiogenesis, thereby suppress the procession of BC. In this review, the therapeutic effects and the molecular mechanisms of ginsenosides on BC will be summarized. And the combination strategy of ginsenosides with other drugs on BC will also be discussed. In addition, epigenetic changes, especially microRNAs (miRNAs) targeted by ginsenosides in the treatment of BC are clarified.

MicroRNAs are small non-coding RNAs that play important roles in gene regulation by influencing the translation and longevity of various target mRNAs and the expression of various target genes as well as by modifying histones and DNA methylation of promoter sites. Consequently, when dysregulated, microRNAs are involved in the development and progression of a variety of diseases, including cancer, by affecting cell growth, proliferation, differentiation, migration, and apoptosis. Preparations from the dried root and rhizome of Salvia miltiorrhiza Bge (Lamiaceae), also known as red sage or danshen, are widely used for treating cardiovascular diseases. Accumulating data suggest that certain bioactive constituents of this plant, particularly tanshinones, have broad antitumor effects by interfering with microRNAs and epigenetic enzymes. This paper reviews the evidence for the antineoplastic activities of S. miltiorrhiza constituents by causing or promoting cell cycle arrest, apoptosis, autophagy, epithelial-mesenchymal transition, angiogenesis, and epigenetic changes to provide an outlook on their future roles in the treatment of cancer, both alone and in combination with other modalities.

The circulatory system is a closed conduit system throughout the body and consists of two parts as follows: the cardiovascular system and the lymphatic system. Hematological malignancies usually grow and multiply in the circulatory system, directly or indirectly affecting its function. These malignancies include multiple myeloma, leukemia, and lymphoma. O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) regulates the function and stability of substrate proteins through O-GlcNAc modification. Abnormally expressed OGT is strongly associated with tumorigenesis, including hematological malignancies, colorectal cancer, liver cancer, breast cancer, and prostate cancer. In cells, OGT can assemble with a variety of proteins to form complexes to exercise related biological functions, such as OGT/HCF-1, OGT/TET, NSL, and then regulate glucose metabolism, gene transcription, cell proliferation, and other biological processes, thus affecting the development of hematological malignancies. This review summarizes the complexes involved in the assembly of OGT in cells and the role of related OGT complexes in hematological malignancies. Unraveling the complex network regulated by the OGT complex will facilitate a better understanding of hematologic malignancy development and progression.

To elucidate the molecular mechanisms underlying the therapeutic activity of ginsenoside Rg3 (Gs-Rg3) in the context of hepatocellular carcinoma (HCC). Methods Relevant databases were searched to identify protein targets that were both dysregulated and implicated in HCC, as well as targeted by Gs-Rg3. Generation of a protein-protein interaction network facilitated the selection of connected nodes for the construction of a shared disease- and drug-target interaction network model, and topological analysis identified the most highly connected nodes. Targets were annotated with their associated Gene Ontology terms, followed by Kyoto Encyclopedia of Genes and Genomes biological pathway enrichment analysis. In vitro experiments using 2 hours CC cell lines (Bel-7402 and HCCLM3) were performed to investigate the impact of Gs-Rg3 on cell proliferation, viability, cell cycle, cyclin D1 and sirtuin 2 (SIRT2) levels, and global cellular histone acetylation (specifically H3K18ac and H4K16ac). Results Network pharmacology suggested that Gs-Rg3 synergistically targets multiple proteins and pathways relevant to HCC pathogenesis, including those involved in cell cycle and proliferation. In vitro experiments confirmed that Gs-Rg3 dose-dependently inhibits cell proliferation and viability; induces G1 phase cell cycle arrest; decreases cyclin D1, cyclin-dependent kinase 2 (CDK2), and SIRT2 levels; and enhances global H3K18ac and H4K16ac. Conclusions Hypotheses derived from the network analysis were confirmed in vitro. Gs-Rg3 induces G1 phase cell cycle arrest, concomitant with decreased cyclin D1 and CDK2 levels, suggesting a possible mechanism for inhibiting proliferation. In addition, Gs-Rg3 decreases SIRT2 levels, concomitant with enhanced global H3K18ac and H4K16ac. These findings provide a theoretical basis and a support for further preclinical study of the safety and antineoplastic molecular mechanisms of Gs-Rg3, with the goal of eventual clinical translation.

Cryptotanshinone (CPT) is the main pharmacologically active component of Salvia miltiorrhiza Bunge, and has been demonstrated to have inhibitory effects on a variety of cancer cell types. However, the target(s) of CPT in colorectal cancer (CRC) cells are still to be identified. The aim of this study was to investigate the molecular mechanism of CPT-induced apoptosis in CRC cells. Transcriptome sequencing revealed that 1234 genes were differentially expressed in CPT-treated SW480 cells compared with vehicle control, which were associated with signaling pathways such as PI3K/AKT, Pathways in cancer and biological processes include cell proliferation and mitochondrial function. CCK-8, colony formation assay, and CRC tumor xenograft models suggested that CPT suppressed the colony formation ability and inhibited proliferation of CRC cells in vitro and in vivo, while flow cytometry indicated that CPT arrested the cell cycle in S phase. JC-1, Hoechst and Western blot analysis indicated that CPT promoted apoptosis in CRC cells and triggered alterations in mitochondrial membrane potential. In addition, database analysis showed that high SIRT3 expression in CRC and high SIRT3 expression in CRC was associated with shorter survival times. Immunofluorescence, Western blot, and molecular docking confirmed that CPT was able to target SIRT3 and downregulate SIRT3 protein levels in a concentration-dependent manner. In summary, CPT inhibits SIRT3 protein expression and inhibits CRC proliferation in vitro and in vivo.

Curative therapies with fewer adverse effects are required for cancer treatment. Medicinal plants represent a promising source of novel therapeutic candidates. We employed network pharmacology to predict potential molecular mechanisms of salvia root-derived tanshinone IIA (Tan IIA) in the treatment of colorectal cancer (CRC), followed by empirical validation. The Traditional Chinese Medicine System Pharmacology (TCMSP), DrugBank, and GeneCards databases were queried to identify overlapping Tan IIA (therapeutic)- and CRC (disease)-relevant protein targets. Cytoscape and STRING were used to generate component-target and protein-protein interaction (PPI) networks, respectively, and topology analysis identified highly connected nodes within the latter. Target proteins were subjected to gene ontology (GO)-based biological process annotation using DAVID, and to biological pathway enrichment analysis using the Kyoto encyclopedia and genome (KEGG) database. Enriched biological processes included cell cycling and proliferation, and enriched KEGG pathways included neuroactive ligand-receptor interaction, PI3K-Akt, and cancer. Network pharmacology results predicted that Tan IIA impacts multiple targets and pathways, but that its therapeutic effect is predominantly attributable to cell cycle regulation, inhibition of cell proliferation, and induction of apoptosis. Investigation of the in vitro impact of Tan IIA on proliferation, viability, and cell cycling of 2 hoursuman CRC cell lines (SW480 and SW620), using the CCK-8 method and flow cytometry, demonstrated that Tan IIA significantly inhibits cell proliferation via inducing cell cycle arrest in the G2/M phase. Network pharmacology-predicted hypotheses were thus empirically validated, providing a basis for in-depth study of the therapeutic mechanisms of Tan IIA in the context of CRC.