Cytotoxic sesquiterpene lactones and lignans from Cousinia turkmenorum Bornm (Asteraceae).

Seven sesquiterpene lactones, chlorophyssopifolin E (1), aguerin B (2), repdiolide triol (3), solistitiolide (4), aitchisonolide (5), sinicin B (6), cynaropicrin (7), along with four lignans arctigenin (8), arctiin (9), matairesinol (10), and matairesinoside (11) were isolated for the first time from the aerial parts of Cousinia turkmenorum Bornm. Among the isolated compounds, aguerin B (2) showed the most cytotoxic activity against MCF7 cell lines with IC50 value of 18.9 µM. Findings of this study could be useful for the development of new anticancer agents from nature.

Comparative proteomics study of proteins involved in induction of higher rates of cell death in mitoxantrone-resistant breast cancer cells MCF-7/MX exposed to TNF-α.

OBJECTIVES: Resistance to medications is one of the main complications in chemotherapy of cancer. It has been shown that some multidrug resistant cancer cells indicate more sensitivity against cytotoxic effects of TNF-α compared to their parental cells. Our previous findings indicated vulnerability of the mitoxantrone-resistant breast cancer cells MCF-7/MX to cell death induced by TNF-α compared to the parent cells MCF-7. In this study, we performed a comparative proteomics analysis for identification of proteins involved in induction of higher susceptibility of MCF-7/MX cells to cytotoxic effect of TNF-α. MATERIALS AND METHODS: Intensity of protein spots in 2D gel electrophoresis profiles of MCF-7 and MCF-7/MX cells were compared with Image Master Platinum 6.0 software. Selected differential protein-spots were identified with MALDI-TOF/TOF mass spectrometry and database searching. Pathway analyses of identified proteins were performed using PANTHER, KEGG PATHWAY, Gene MANIA and STRING databases. Western blot was performed for confirmation of the proteomics results. RESULTS: Our results indicated that 48 hr exposure to TNF-α induced 87% death in MCF-7/MX cells compared to 19% death in MCF-7 cells. Forty landmarks per 2D gel electrophoresis were matched by Image Master Software. Six proteins were identified with mass spectrometry. Western blot showed that 14-3-3γ and p53 proteins were expressed higher in MCF-7/MX cells treated with TNF-α compared to MCF-7 cells treated with TNF-α. CONCLUSION: Our results showed that 14-3-3 γ, prohibitin, peroxiredoxin 2 and P53 proteins which were expressed differentially in MCF-7/MX cells treated with TNF-α may involve in the induction of higher rates of cell death in these cells compared to TNF-α-treated MCF-7 cells.

LC-ESI/LTQOrbitrap/MS/MS and GC-MS profiling of Stachys parviflora L. and evaluation of its biological activities.

The use of some Stachys genus as herbal remedies is known and the aerial parts have a pharmaceutical interest, being used in Anatolia and Iran as wild tea. In this study, chemical composition, antimicrobial, antioxidant, and antiproliferative activities of the methanolic extract and essential oil (EO) of Stachys parviflora L. (S. parviflora) were evaluated. Qualitative analysis of metabolites of S. parviflora methanolic extract was studied using liquid chromatography coupled to high resolution mass spectrometry (LC-ESI/LTQOrbitrap/MS), evidencing the presence of phenolic acids and flavonoids derivatives. The EO was analyzed using gas chromatography coupled to mass spectrometry (GC/MS). Eighty-seven compounds were characterized in the EO of S. parviflora, of which α-terpenyl acetate (23.6%), ß-caryophyllene (16.8%), bicyclogermacrene (9.3%), spathulenol (4.9%) and α-pinene (4.2%) were found to be the major components. The highest antimicrobial effect of EO was found to S. aureus and B. cereus (MIC = 0.01 µg/ml), while the highest activity of extract was against B. cereus (MIC = 125 µg/ml). The methanolic extract exhibited strong antioxidant activity in DPPH (IC50 = 76.87 µg/ml) and ß-carotene/linoleic acid assay (BCB, IC50 = 188.47 µg/ml) methods. Furthermore, in vitro cytotoxicity evaluation against three cell lines namely human ovarian carcinoma (A2780), human colon carcinoma (HCT), and mouse melanoma cell line (B16F10), showed an anti-proliferative activity of the EO ranging from IC50 value 30.95 µg/ml to 16.55 µg/ml. The results from this study have demonstrated the promising cytotoxic, antibacterial, and antifungal properties of S. parviflora, which could have wide potential applications in food and pharmaceutical industries.

Crosstalk in cancer resistance and metastasis.

The main obstacles that lead to clinical failure in cancer treatment are the development of resistant to chemotherapy and a rise in invasive characteristics in cancer tumor cells due to prolonged chemotherapeutic processes. Recent studies have revealed some evidence about the existence of a direct relationship between development of drug resistance and triggering of invasive capability in tumor cells. Therefore, devising and application of chemotherapeutic procedures that are not prone to the development of chemotherapy resistance are necessary. Here, we focus on CD147, CD44, ANAX2, P-gp, MMPs, and UCH-L1 proteins involved in the crosstalk between metastasis and cancer treatment. We think that further structural and functional analysis of these proteins may direct scientists towards designing highly effective chemotherapy procedures.

Curcumin as an Adjunct Therapy and microRNA Modulator in Breast Cancer.

BACKGROUND: Pathogenesis of breast cancer is paralleled by distinct alterations in the expression profile of several microRNAs (miRNAs). Recent studies have shown that miRNAs can serve as diagnostic and prognostic markers, and also as therapeutic targets in breast cancer. Curcumin is a biologically active dietary polyphenol that has emerged with strong anti-tumor properties that are also documented in breast cancer. METHODS: A multi-database electronic search was performed to provide an overview of curcumin as an adjunct therapy and miRNA modulator in breast cancer and highlight the significance of observations for the treatment of cancer therapies. RESULTS: The putative anti-tumor properties of curcumin are mediated by diverse mechanisms including inhibition of cell proliferation, metastasis, migration, invasion and angiogenesis, and induction of G2/M cell cycle arrest, apoptosis and paraptosis. Recent evidence implies that curcumin can interact with several oncogenic and tumorsuppressive miRNAs involved in different stages of breast cancer. In this context, up-regulation of miR181b, miR-34a, miR-16, miR-15a and miR-146b-5p, and down-regulation of miR-19a and miR-19b have been shown following the treatment of several breast cancer cell lines with curcumin. These effects lead to the suppression of tumorigenesis and metastasis, and induction of apoptosis. CONCLUSION: Curcumin appears as an important miRNA modulator in breast cancer. However, further investigations are warranted to elucidate the impact of curcumin on miRNA transcriptome profile of breast cancer and the resulting impact of experimental models.

Death inducing and cytoprotective autophagy in T-47D cells by two common antibacterial drugs: sulphathiazole and sulphacetamide.

The broad spectrum of the pharmacological effects of sulphonamide family of drugs motivated us to investigate the cellular mechanisms for anti-cancer effects of sulphathiazole and sulphacetamide on T-47D breast cancer cells. Fluorescent microscopy, flow cytometric analysis, caspase-3 activity and DNA fragmentation assays were used to detect apoptosis. The distribution of the cells among different phases of the cell cycle was measured by flow cytometry. The expression of several genes with important roles in some critical cellular pathways including apoptosis, mTOR/AKT pathway and autophagy were determined by real-time RT-PCR analysis. Sulphathiazole and sulphacetamide induced anti-proliferative effects on T-47D cells were independent of apoptosis and cell cycle arrest. The overexpression of critical genes involved in autophagy including ATG5, p53 and DRAM indicated that the main effect of the drug-induced anti-proliferative effects was through induction of autophagy. This process was induced in two different forms, including death inducing and cytoprotective autophagy. Sulphathiazole treatment was followed by higher expression of p53/DRAM and downregulation of Akt/mTOR pathway resulting in death autophagy. In contrast, sulphacetamide treatment lowered expression of p53/DRAM pathway in parallel with upregulation of Akt/mTOR pathway promoting cytoprotective autophagy. The results indicated that autophagy is the main mechanism mediating the anti-cancer effects of sulphathiazole and sulphacetamide on T-47D cells. Alignment of the p53 and DRAM expression along with activation level of Akt survival pathway therefore determines the type of autophagy that occurs.