In Silico Evaluation of Natural Compounds for an Acidic Extracellular Environment in Human Breast Cancer

Abstract

The survival rates for breast cancer (BC) have improved in recent years, but resistance, metastasis, and recurrence still remain major therapeutic challenges for BC. The acidic tumor microenvironment (TME) has attracted attention because of its association with tumorigenesis, metastasis, drug resistance, and immune surveillance. In this study, we evaluated natural compounds from traditional herbal medicine used to treat cancer that selectively target genes regulated by extracellular acidosis. We integrated four transcriptomic data including BC prognostic data from The Cancer Genome Atlas database, gene expression profiles of MCF-7 cells treated with 102 natural compounds, patterns of gene profiles by acidic condition, and single-cell RNA-sequencing from BC patient samples. Bruceine D (BD) was predicted as having the highest therapeutic potential, having an information gain (IG) score of 0.24, to regulate reprogrammed genes driven by acidosis affecting the survival of BC patients. BD showed the highest IG on EMT (IG score: 0.11) and invasion (IG score: 0.1) compared to the other phenotypes with the CancerSEA database. BD also demonstrated therapeutic potential by interfering with the tumor cell–TME interactions by reducing the amyloid beta precursor protein and CD44 expression. Therefore, BD is a potential candidate to target the acidic TME induced metastatic process in BC.

Bruceine D Identified as a Drug Candidate against Breast Cancer by a Novel Drug Selection Pipeline and Cell Viability Assay

“…In addition to the cell viability decrease, bruceine D was further shown to reduce the migration and invasion of MDA-MB-231 cells by upregulating the expression of E-cadherin and downregulating vimentin, suggesting a bruceine D-dependent reversal of EMT in these cells [43]. More recently, evidence was indeed provided that bruceine D treatment led to an upregulation of genes that are negatively correlated with EMT, and to a downregulation of genes that are positively correlated with EMT [66].…”

Mapping and Validation of scRNA-Seq-Derived Cell-Cell Communication Networks in the Tumor Microenvironment

“…First applied to the wound healing microenvironment, CellChat has shown promise in the characterization of malignant and immunotherapy-altered signaling in glioblastoma ( 58 ), esophageal squamous cell carcinoma ( 41 ), gastric cancer ( 59 ), and breast cancer ( 60 ). When compared directly to CellPhoneDB ( 55 ) across four mouse skin scRNA-seq datasets, CellChat achieved a slightly better true positive rate, a lower false positive rate, and higher accuracy.…”

Advances in Plants-Derived Bioactives for Cancer Treatment

“…Additionally, it is noteworthy that in vivo tannic acid was capable of significantly delaying tumor growth without exerting liver and kidney toxicity. In the same line, Bakshi et al [ 5 ] addressed the ability of crocin to inhibit angiogenesis and metastasis in colon cancer cell lines. As their main findings, the authors stated that crocin markedly decreased the viability of cancer cell lines exerting any toxicity in normal counterparts, mostly through the inhibition of cell migration, invasion, and tube formation in a dose-dependent fashion.…”

“…As their main findings, the authors stated that crocin markedly decreased the viability of cancer cell lines exerting any toxicity in normal counterparts, mostly through the inhibition of cell migration, invasion, and tube formation in a dose-dependent fashion. Concomitantly, these findings were observed in vivo and stated that crocin inhibited angiogenesis and colorectal cancer metastasis through the modulation of nuclear factor κappa B (NF-κB) and blockage of tumor necrosis factor α (TNF-α)/NF-KB/VEGF pathways [ 5 ].…”