Project description:Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. TNBC exists widely reprogrammed lipid metabolism, and its metabolic-associated proteins and oncometabolites are promising as potential therapeutic targets. Dandelion (Taraxacum mongolicum) is a classical herbal medicine used to treat breast diseases based on traditional Chinese medicine theory and was reported to have antitumor effects and lipid regulatory capacities. Our previous study showed that dandelion extract was effective against TNBC. However, whether dandelion extract could regulate the lipid metabolisms of TNBC and exert its antitumor effects via interfering with lipids metabolism remained unclear. In this study, an integrated approach combined with network pharmacology and multi-omics techniques (including proteomics, metabolomics, and lipidomics) was performed to investigate the potential regulatory mechanisms of dandelion extract against TNBC. We first determined the antitumor effects of dandelion extract in vitro and in vivo. Then, network pharmacology analysis speculated the antitumor effects involving various metabolic processes, and the multi-omics results of the cells, tumor tissues, and plasma revealed the changes in the metabolites and metabolic-associated proteins after dandelion extract treatment. The alteration of glycerophospholipids and unsaturated fatty acids were the most remarkable types of metabolites. Therefore, the metabolism of glycerophospholipids and unsaturated fatty acids, and their corresponding proteins CHKA and FADS2, were considered the primary regulatory pathways and biomarkers of dandelion extract against TNBC. Subsequently, experimental validation showed that dandelion extract decreased CHKA expression, leading to the inhibition of the PI3K/AKT pathway and its downstream targets, SREBP and FADS2. Finally, the molecular docking simulation suggested that picrasinoside F and luteolin in dandelion extract had the most highly binding scores with CHKA, indicating they may be the potential CHKA inhibitors to regulate glycerophospholipids metabolisms of TNBC. In conclusion, we confirmed the antitumor effects of dandelion extract against TNBC cells in vitro and demonstrated that dandelion extract could interfere with glycerophospholipids and unsaturated fatty acids metabolism via downregulating the CHKA expression and thus inhibiting PI3K/AKT/SREBP/FADS2 axis.
Project description:We investigated the effects of the crude extract of a South African medicinal plant, Cotyledon orbiculata, on cell survival of colon (HCT116) cancer cell lines. Using RNASeq, we discovered that the extract interfered with mRNA regulatory pathways. Here, we found that the extract of Cotyledon orbiculata, a South African medicinal plant, had an anti-proliferative effect in cancer cells, mediated by apoptosis induced by alternative splicing of hnRNPA2B1 and BCL2L1.
Project description:Using LC-MS/MS, we analyzed ECM-enriched samples obtained from 1) human triple-negative breast cancer samples and matched adjacent normal mammary gland tissues, and 2) disease-free omentum from patient with non-metastatic ovarian cancer and high-grade- serous-ovarian- cancer-derived omental metastasis samples. We conducted the LC-MS/MS analysis on peptides obtained after solubilizing ECM-enriched samples using different methods (crude ECM extract, urea-soluble extract, urea-insoluble extract) and submitted to basic-reversed- phase separation or not.
Project description:Supercritical rosemary extract (containing 16.90% carnosic acid, 1.90% carnosol and 13.59% volatile compounds) showed antitumor activity on colon cancer cells in vitro. We treated colon cancer cells with the extract and we employed whole genome microarray expression profiling to identify genes potentially involved in its antitumor mechanism of action.
Project description:The traditional Chinese medicine Jinfukang (JFK) has been shown as a valuable drug for the non-small cell lung cancer (NSCLC) patients. Although clinically effective, the underlining mechanism remains unclear. Here, we performed RNA-seq assays for study the antitumor mechanisms of JFK ethanol extract on lung cancer cell line A549.
Project description:This project aimed to explore novel anticancer therapeutics from products of parasite since several data related to benefits from the T. spiralis infection have been documented. We validated antitumor activity of T. spiralis infective larval extract and extricate the parasite-derived-antitumor peptide. We found that larval extract exerted antitumor activity to three types of carcinoma cells including hepatocellular carcinoma HepG2, ovarian cancer SK-OV-3, and lung adenocarcinoma A549. Interestingly, it displayed the most antitumor effect to HepG2 cells. Using proteomic and bioinformatic approaches, three putative anticancer peptides were identified from T. spiralis infective larval extract. One of these peptides showed a dose-dependent-anti-HepG2 effect by inducing ROS accumulation, leading to inhibition of the cell proliferation. Our data indicate potential application of the larval extract-derived antitumor peptide as a complementary agent for human hepatoma treatment and highlight a positive aspect of parasite apart from its deleterious effect.
Project description:To investigate the effects of transgenic lines L6 and L7 tomato fruits on total expression profile of MCF-7 breast cancer cells, we treated MCF-7 cells with 1 ug/ml of tomato fruit extract for 24 hours and compare it with wild type tomato fruit extract Objectives for this study included the identification of genes that were up or down-regulated at the transcriptional level in MCF-7 cells treated with transgenic lines L6 and L7 tomatofruit extract and compare it to wild type tomato fruit extract.
Project description:Mufudza2012 - Estrogen effect on the dynamics
of breast cancer
This deterministic model shows the
dynamics of breast cancer with immune response. The effects of
estrogen are incorporated to study its effects as a risk factor for
the disease.
This model is described in the article:
Assessing the effects of
estrogen on the dynamics of breast cancer.
Mufudza C, Sorofa W, Chiyaka
ET.
Comput Math Methods Med 2012; 2012:
473572
Abstract:
Worldwide, breast cancer has become the second most common
cancer in women. The disease has currently been named the most
deadly cancer in women but little is known on what causes the
disease. We present the effects of estrogen as a risk factor on
the dynamics of breast cancer. We develop a deterministic
mathematical model showing general dynamics of breast cancer
with immune response. This is a four-population model that
includes tumor cells, host cells, immune cells, and estrogen.
The effects of estrogen are then incorporated in the model. The
results show that the presence of extra estrogen increases the
risk of developing breast cancer.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000642.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
Project description:Supercritical rosemary extract (containing 16.90% carnosic acid, 1.90% carnosol and 13.59% volatile compounds) showed antitumor activity on colon cancer cells in vitro. We treated colon cancer cells with the extract and we employed whole genome microarray expression profiling to identify genes potentially involved in its antitumor mechanism of action. We analyzed gene expression of colon cancer SW620 cells after treating during 48h with supercritical rosemary extract at concentrations that cause 50% inhibition of cell viability (30 M-NM-<g/mL), citostatic effect (60 M-NM-<g/mL) and 50% cell death (100 M-NM-<g/mL), in comparison to control cells (0 M-NM-<g/mL). Two independent experiments were performed in triplicate. Each sample is the pool of the triplicates of one of the experiments (a or b) at the indicated concentration.
Project description:Extracts from the rhizome of Cimicifuga racemosa (black cohosh) are increasingly popular as herbal alternative to hormone replacement therapy (HRT) for the alleviation of postmenopausal disorders. However, the molecular mode of action and the active principles are presently not clear. Previously published data have been largely contradictory. We, therefore, investigated the effects of a lipophilic Cimicifuga rhizome extract on the ER+ breast cancer MCF-7 cells at transcriptional level in comparision to 17beta-estradiol and the ER antagonist tamoxifen. With the extract 431 genes were regulated more than 1.5 fold. The overall expression pattern differed from those of 17β-estradiol or the estrogen receptor antagonist tamoxifen. We observed an enrichment of genes in an anti-proliferative and apoptosis-sensitizing manner, together with an increase of mRNAs coding for gene products involved in several stress response pathways. Regulated genes of these functional groups were highly overrepresented among all regulated genes. Various transcripts coding for oxidoreductases were induced, as for example the cytochrome P450 family members 1A1 and 1B1. In addition, some transcripts associated with antitumor but also tumor-promoting activity were regulated. Experiment Overall Design: MCF-7 cells were treated for 24 h with a lipophilic (dichloromethane) Cimicifuga rhizome extract, 17beta-estradiol, tamoxifen and the solvent control (DMSO 0,1%) in duplicate