aurapten and Breast-Neoplasms

Angiogenesis is the most important challenge in breast cancer treatment. Recently, scientists become interesting in rare natural products and intensive researches was performed to identify their pharmacological profile. Auraptene shows helpful effects such as cancer chemo-preventive, anti-inflammatory, anti-oxidant, immuno-modulatory. In this regard, we investigated the anti-angiogenesis effect of Auraptene in. Auraptene treatment led to reduction in cell viability of MDA-MB-231 in a concentration-dependent manner. Also, we observed change in the number of tubes or branches formed by cells incubated with 40 and 80 μM Auraptene. Auraptene effect the gene expression of important gene related to angiogenesis (VEGF, VEGFR2, COX2, IFNɣ). Moreover, the western blot data exhibited that Auraptene effect the protein expression of VCAM-1 and TNFR-1.. Overall, this study shows that Auraptene significantly suppressed angiogenesis via down-regulation of VEGF, VEGFR2, VCAM-1, TNFR-1, COX-2 and up-regulation of IFNγ.

Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Coumarins; Female; Heterografts; Humans; Neovascularization, Pathologic

Breast cancer is a common malignant tumor in women with limited treatment options and multiple side effects. Today, the anti-cancer properties of natural compounds have attracted widespread attention from researchers worldwide.. In this study, we treated 4T1 tumor-bearing Balb/c mice with intraperitoneal injection of Auraptene, paraffin oil, and saline as two control groups. Body weight and tumor volume were measured before and after treatment. Hematoxylin and eosin (H & E) staining and immunohistochemistry of Ki-67 were used as markers of proliferation. In addition, ELISA assays were performed to assess serum IFN-γ and IL-4 levels.. There was no significant change in body weight in all animal groups before and after treatment. 10 days after the last treatment, Auraptene showed its anti-cancer effect, which was confirmed by the smaller tumor volume and H & E staining. In addition, Ki-67 expression levels were significantly reduced in tumor samples from the Auraptene-treated group compared to the paraffin oil and saline-treated groups. In addition, in tumor-bearing and normal mice receiving Auraptene treatment, IL-4 serum production levels were reduced, while serum levels of IFN-γ were significantly up-regulated in tumor-bearing mice after Auraptene treatment.. In the case of inhibition of tumor volume and Ki-67 proliferation markers, Auraptene can effectively inhibit tumor growth in breast cancer animal models. In addition, it might increases Th1 and CD8 + T cell responses after reducing IL-4 serum levels and IFN-γ upregulation, respectively. However, further research is needed to clarify its mechanism of action.

Topics: Allografts; Animals; Antineoplastic Agents; Biological Products; Biomarkers, Tumor; Breast Neoplasms; Cell Line, Tumor; Coumarins; Cytokines; Disease Models, Animal; Female; Immunohistochemistry; Mice; Mice, Inbred BALB C; Molecular Structure; Tumor Burden

Auraptene (AUR), a natural bioactive prenyloxy coumarin, is a highly pleiotropic molecule that can bind to the MT1 receptor and can effectively reduce the proliferation and migration of breast cancer cells. Cisplatin (CDDP), as the first synthetic platinum-based anticancer drug, is widely used in the clinic due to its definite mechanism and therapeutic effect on diverse tumors. However, both of AUR and CDDP exhibit some disadvantages when used alone, including poor solubility, low bioavailability, lack of selectivity and systemic toxicity when they are used singly.. Therefore, the biodegradable materials hyaluronic acid (HA) and β-cyclodextrin derivative (mono-(6-amino-mono-6-deoxy)-β-CD, CD) were employed as carriers to load AUR and CDDP to form nanogel (. With the help of the CDDP-crosslinked CD-loaded structure, the newly synthesized nanogel exhibited excellent physiological stability and fluorescence effects. The release of AUR and CDDP was affected by the pH value, which was beneficial to the selective release in the tumor microenvironment. Cell experiments in vitro demonstrated that the nanogel could be selectively internalized by MCF-7 cells and exhibited low cytotoxicity to HK-2 cells. Antitumor experiments in vivo showed that the nanogel have better antitumor effects and lower systemic toxicity.. Based on these, the nanogel loaded with AUR and CDDP have the potential for targeted delivery against breast cancer.

Topics: Animals; Breast Neoplasms; Cell Death; Cisplatin; Coumarins; Drug Carriers; Drug Liberation; Endocytosis; Female; Hemolysis; Humans; Hyaluronic Acid; Hydrogen-Ion Concentration; MCF-7 Cells; Mice, Inbred BALB C; Mice, Nude; Nanogels; Organ Specificity; Particle Size; Polyethylene Glycols; Polyethyleneimine; Rabbits; Spectrometry, Fluorescence; Spectroscopy, Fourier Transform Infrared

Oxyprenylated compounds (i.e., ferulic acid and coumarin derivatives) demonstrate neuroprotection and anticancer properties as reported in previous studies. We have tested the affinity of oxyprenylated ferulic acid (1-4) and umbelliferone derivatives (5-11) to melatonin receptors as well as their antiproliferation and antimigratory properties against breast cancer (BC) cell lines. All the compounds except for ferulic acid, boropinic acid, and umbelliferone had binding affinities to melatonin receptors in the nM to μM range, and both auraptene and umbellinprenin reduced BC cell proliferation and migration in phenotypically diverse BC including triple negative.

Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Coumaric Acids; Coumarins; Female; Humans; MCF-7 Cells; Mice; Receptor, Melatonin, MT1; Umbelliferones

Bioassay-guided isolation and subsequent structure elucidation of a Bael tree Aegle marmelos lipid extract yielded two unstable acylated geranyloxycoumarin mixtures (1-2), six geranyloxycoumarins (3-8), (+)-9'-isovaleroxylariciresinol (9), and dehydromarmeline (10). In a T47D cell-based reporter assay, 1 and 2 potently inhibited hypoxia-induced HIF-1 activation (IC50 values 0.18 and 1.10 μgmL(-1), respectively). Insufficient material and chemical instability prevented full delineation of the fatty acyl side chain olefin substitution patterns in 1 and 2. Therefore, five fatty acyl geranyloxycoumarin ester derivatives (11-15) were prepared from marmin (3) and commercial fatty acyl chlorides by semisynthesis. The unsaturated C-6' linoleic acid ester derivative 14 that was structurally most similar to 1 and 2, inhibited HIF-1 activation with comparable potency (IC50 0.92 μM). The octanoyl (11) and undecanoyl (12) ester derivatives also suppressed HIF-1 activation (IC50 values 3.1 and 0.87 μM, respectively). Mechanistic studies revealed that these geranyloxycoumarin derivatives disrupt mitochondrial respiration, primarily at complex I. Thus, these compounds may inhibit HIF-1 activation by suppressing mitochondria-mediated hypoxic signaling. One surprising observation was that, while less potent, the purported cancer chemopreventive agent auraptene (8) was found to act as a mitochondrial poison that disrupts HIF-1 signaling in tumors.

Topics: Aegle; Antineoplastic Agents, Phytogenic; Breast; Breast Neoplasms; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell Respiration; Cell Survival; Coumarins; Dietary Supplements; Female; Humans; Hypoxia-Inducible Factor 1; Mitochondria; Plant Extracts