peoniflorin and Breast-Neoplasms

Paeoniflorin, a representative pinane monoterpene glycoside in plants of Paeoniaceae family, possesses promising anticancer activities on diverse tumours. This paper summarized the advance of Paeoniflorin on cancers in vivo and in vitro, discussed the related molecular mechanisms, as well as suggested some perspectives of the future investigations.. Anticancer activities of paeoniflorin have been comprehensively investigated, including liver cancer, gastric cancer, breast cancer, lung cancer, pancreatic cancer, colorectal cancer, glioma, bladder cancer and leukaemia. Furthermore, the potential molecular mechanisms corresponding to the antitumour effects of Paeoniflorin might be related to the following aspects: inhibition of tumour cell proliferation and neovascularization, induction apoptosis, and inhibition of tumour invasion and metastasis.. Paeoniflorin has wide spectrum antitumour activities; however, in vivo and clinical investigations on antitumour effect of Paeoniflorin are lacking which should be focused on further studies. Our present review on antitumour effects of Paeoniflorin would be beneficial for the further molecular mechanisms study, candidate antitumour drug development and clinical research of Paeoniflorin in the future.

Topics: Animals; Apoptosis; Breast Neoplasms; Cell Proliferation; Colorectal Neoplasms; Glioma; Glucosides; Humans; Leukemia; Liver Neoplasms; Lung Neoplasms; Monoterpenes; Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Urinary Bladder Neoplasms

Paeoniflorin (PF), a compound found in Paeonia lactiflora and Paeonia suffruticosa, has anticancer potential, particularly in inhibiting migration and invasion, the resistant cancer cells hallmarks. To date, the mechanism of overcoming tamoxifen resistance in breast cancer is not yet elucidated. This research aims to explore the potential target of PF as a co-treatment for circumventing breast cancer resistance to tamoxifen with a genomic understanding-bioinformatics.. Microarray data originating from GSE67916 and GSE85871 in the NCBI GEO database was analyzed to obtain differentially expressed genes (DEGs). Further analyses were performed on DEGs using the DAVID v6.8, STRING-DB v11.0, the Cytoscape, and cBioportal. Gene expression analysis validation in breast cancer cells and tamoxifen-resistant breast cancer cells was accomplished using GEPIA and ONCOMINE databases. Survival rate analysis of selected genes was conducted using Kaplan-Meier.. We obtained 175 DEGs from the two samples (tamoxifen-resistant and paeoniflorin-treated). DEG involves in 70 biological processes, 26 cellular components, and 18 molecular functions, and three pathways relevant to breast cancer. The PPI network analysis and hub genes selection obtained 10 genes with the highest degree scores. Genetic changes for selected genes, including IFNB1, CDK6, FGFR2, OAS1, BCL2, and STAT2 were found from 0.5% to 7% of the case population per patient case. Additional analysis using cBioportal revealed FGFR signaling pathway through Ras is important for the PF mechanism in circumventing breast cancer resistance to tamoxifen. ONCOMINE and GEPIA analysis emphasized the importance of selected genes in the tamoxifen-resistance mechanism.. PF has potential to be used as a co-treatment for circumventing breast cancer resistance to tamoxifen by targeting FGFR2 signaling, but further validation is needed.

Topics: Antineoplastic Agents; Breast Neoplasms; Computational Biology; Databases, Genetic; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genomics; Glucosides; Humans; Kaplan-Meier Estimate; Monoterpenes; Protein Interaction Maps; Receptor, Fibroblast Growth Factor, Type 2; Signal Transduction; Tamoxifen

Paeoniflorin (Pae) possesses anti-tumor activity in various malignancies. However, it is unclear whether Pae plays a sensitizer role in breast cancer (BC) and the molecular mechanisms involved in this process. Our oligonucleotide microarray revealed that microRNA (miR)-15b is the most significantly downregulated miRNA in MCF-7/4-hydroxytamoxifen (4-OHT) cells treated with Pae. This paper summarized the relevance of Pae in BC cell endocrine resistance to tamoxifen (Tam) and the molecular mechanisms involved miR-15b expression.. 4-OHT-resistant BC cell lines were developed and treated with different concentrations of Pae. Flow cytometry, lactose dehydrogenase activity, caspase-3 activity, colony formation, and EdU assays were carried out to assess the impact of Pae on BC cells. Differentially expressed miRNAs in BC cells treated with Pae were analyzed by microarray. Targeting mRNAs of screened miR-15b as well as the binding of forkhead box O1 (FOXO1) to the cyclin D1 (CCND1) promoter sequence were predicted through bioinformatics analysis. Finally, the expression of β-catenin signaling-related genes in cells was detected by Western blotting.. Pae (100 μg/mL) inhibited the clonality and viability of BC cells, while enhancing apoptosis in vitro. Pae also repressed miR-15b expression. Overexpression of miR-15b restored the growth and resistance of BC cells to 4-OHT. Moreover, Pae promoted FOXO1 expression by downregulating miR-15b, thereby transcriptionally inhibiting CCND1 and subsequently blocking β-catenin signaling.. Pae inhibits 4-OHT resistance in BC cells by regulating the miR-15b/FOXO1/CCND1/β-catenin pathway.

Topics: Antineoplastic Agents; Apoptosis; beta Catenin; Breast Neoplasms; Cell Proliferation; Cell Survival; Cyclin D1; Down-Regulation; Drug Screening Assays, Antitumor; Female; Forkhead Box Protein O1; Glucosides; Humans; MicroRNAs; Monoterpenes; Tamoxifen; Tumor Cells, Cultured

Breast cancer is one of the most frequently occurring malignant tumors affecting women's health. At least one million new cases are diagnosed each year. Therefore, research that aims to identify strategies that inhibit the growth of breast cancer cells has become a primary worldwide focus. Traditional Chinese medicine (TCM) is regarded as a valuable resource in China, and numerous monomer compositions extracted from TCMs have been demonstrated to exhibit antitumor effects. The present study aimed to determine the impact of paeoniflorin (PF) on breast cancer cell proliferation and invasion, and to explore the mechanisms underlying its effects. Different concentrations of PF were applied to MCF‑7 cells at various time points and the Cell Counting kit‑8 assay was used to determine cell proliferation, a transwell invasion assay was employed to determine cell invasion, reverse transcription‑polymerase chain reaction was used to determine notch homolog‑1 (NOTCH‑1) and Hes family basic helix‑loop helix transcription factor (HES)‑1 mRNA expression levels, and western blotting was used to determine NOTCH‑1 and HES‑1 protein expression levels. The results demonstrated that PF inhibited the proliferation of MCF‑7 cells in a dose‑ and time‑dependent manner. Following treatment with different concentrations of PF, the total number of cells present in the PF‑treated groups was significantly lower when compared with the untreated control group (P<0.05). With increasing doses of PF, the rate of cell invasion significantly decreased, indicating a dose‑dependent association. NOTCH‑1 and HES‑1 mRNA expression levels were reduced when compared with the untreated control group, which reached a statistical significance following treatment with 15 and 30 µM PF (P<0.05). NOTCH‑1 and HES‑1 protein levels demonstrated a similar trend to the mRNA levels, whereby an increase in the concentration of PF was associated with a decrease in NOTCH‑1 and HES‑1 protein expression levels. The results of the present study therefore suggest that PF may inhibit the proliferation and invasiveness of breast cancer cells via inhibition of the NOTCH‑1 signaling pathway.

Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Female; Gene Expression; Glucosides; Humans; MCF-7 Cells; Monoterpenes; Receptor, Notch1; Signal Transduction; Transcription Factor HES-1

Paeoniflorin (PF), one of the major active ingredients of Chinese peony, was reported to possess anti-tumor effect. However, the role of PF in breast cancer remains to be clarified. Therefore, in this context, the present study investigated the effects of PF on breast cancer cell proliferation and invasion, as well as the underlying mechanism. Our results found that PF suppressed the proliferation and invasion of breast cancer cells. We further demonstrated that PF down-regulated the expression of Notch-1; in addition, overexpression of Notch-1 reversed PF-inhibited proliferation and invasion, and knockdown of Notch-1 enhanced PF-inhibited proliferation and invasion in breast cancer cells. In conclusion, the present study suggests that PF inhibits proliferation and invasion of breast cancer cells through suppressing Notch-1 signaling pathway. Therefore, PF may represent a chemopreventive and/or therapeutic agent in the prevention of breast cancer.

Topics: Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Female; Gene Knockdown Techniques; Glucosides; Humans; Monoterpenes; Neoplasm Invasiveness; Receptors, Notch; Signal Transduction