Lasiokaurin Regulates PLK1 to Induce Breast Cancer Cell G2/M Phase Block and Apoptosis.

Aim of the study: To investigate the anti-tumor effects of Lasiokaurin on breast cancer and explore its underlying molecular mechanism. Materials and methods: In this study, MTT assay, plate colony formation assays, soft agar assay, and EdU assay were employed to evaluate the anti-proliferation effects of LAS. Apoptosis and cell cycle distribution were detected by flow cytometry. The molecular mechanism was predicted by performing RNA sequencing and verified by using immunoblotting assays. Breast cancer organiods derived from patient-derived xenografts model and MDA-MB-231 xenograft mouse model were established to assess the effect of LAS. Results: Our study showed that LAS treatment significantly suppressed cell viability of 5 breast cancer cell lines, with the IC50 value of approximately 1-5 µM. LAS also inhibitied the clonogenic ability and DNA synthesis of breast cancer cells, Moreover, LAS induced apoptosis and G2/M cell cycle arrest in SK-BR-3 and MDA-MB-231 cells. Notably, transcriptomic analysis predicted the mechanistic involvement of PLK1 in LAS-suppressed breast cancer progression. Our experiment data further verified that LAS reduced PLK1 mRNA and protein expression in breast cancer, accompanied by downregulating CDC25C and AKT phosphorylation. Ultimately, we confirmed that LAS inhibit breast cancer growth via inhibiting PLK1 pathway in vivo. Conclusions: Collectively, our findings revealed that LAS inhibits breast cancer progression via regulating PLK1 pathway, which provids scientific evidence for the use of traditional Chinese medicine in cancer therapy.

UTP23 Is a Promising Prognostic Biomarker and Is Associated with Immune Infiltration in Breast Cancer.

Breast cancer is one of the malignant tumors with a high incidence and mortality rate among women worldwide, and its prevalence is increasing year by year, posing a serious health risk to women. UTP23 (UTP23 Small Subunit Processome Component) is a nucleolar protein that is essential for ribosome production. As we all know, disruption of ribosome structure and function results in improper protein function, affecting the body's normal physiological processes and promoting cancer growth. However, little research has shown a connection between UTP23 and cancer. We analyzed the mRNA expression of UTP23 in normal tissue and breast cancer using The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, and the protein expression of UTP23 using The Human Protein Atlas (HPA) database. Next, we examined the relationship between UTP23 high expression and Overall Survival (OS) using Kaplan-Meier Plotters and enriched 980 differentially expressed genes in UTP23 high and low expression samples using GO/KEGG and GSEA to identify potential biological functions of UTP23 and signaling pathways that it might influence. Finally, we also investigated the relationship between UTP23 and immune infiltration and examined the effect of UTP23 on the proliferation of human breast cancer cell lines by knocking down UTP23. We found that UTP23 levels in breast cancer patient samples were noticeably greater than those in healthy individuals and that high UTP23 levels were strongly linked with poor prognoses (P = 0.008). Functional enrichment analysis revealed that UTP23 expression was connected to the humoral immune response. Besides, UTP23 expression was found to be positively correlated with immune cell infiltration. Furthermore, UTP23 knockdown has been shown to inhibit the proliferation of human breast cancer cells MDA-MB-231 and HCC-1806. Taken together, our study demonstrated that UTP23 is a promising target in detecting and treating breast cancer and is intimately linked to immune infiltration.

Arnicolide C Suppresses Tumor Progression by Targeting 14-3-3θ in Breast Cancer.

Background: Arnicolide C, which is isolated from Centipeda minima, has excellent antitumor effects. However, the potential impacts and related mechanisms of action of arnicolide C in breast cancer remain unknown. Methods: The viability of breast cancer cells was measured using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and colony formation assays. For analysis of apoptosis and the cell cycle, flow cytometry was used. A molecular docking approach was used to explore the possible targets of arnicolide C. Western blot analysis was used to detect changes in the expression of 14-3-3θ and proteins in related pathways after arnicolide C treatment in breast cancer cells. The anti-breast cancer effect of arnicolide C in vivo was evaluated by establishing cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Results: Arnicolide C inhibited proliferation, increased apoptosis, and induced G1 arrest. In particular, molecular docking analysis indicated that arnicolide C binds to 14-3-3θ. Arnicolide C reduced 14-3-3θ expression and inhibited its downstream signaling pathways linked to cell proliferation. Similar results were obtained in the CDX and PDX models. Conclusion: Arnicolide C can have an anti-breast cancer effect both in vitro and in vivo and can induce cell cycle arrest and increase apoptosis in vitro. The molecular mechanism may be related to the effect of arnicolide C on the expression level of 14-3-3θ. However, the specific mechanism through which arnicolide C affects 14-3-3θ protein expression still needs to be determined.