scholarly journals Long non-coding RNA IGF2-AS represses breast cancer tumorigenesis by epigenetically regulating IGF2

2020 ◽  
pp. 153537022096625
Author(s):  
Yanan Zhang ◽  
Hanbing Yan ◽  
Yan Jiang ◽  
Tao Chen ◽  
Zhijin Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Stage ◽  
Breast Cancer Diagnosis ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cognate Gene ◽  
Non Coding Rnas ◽  
Induced Apoptosis

Long non-coding RNAs are a kind of endogenous ncRNAs with a length of more than 200 bp. Accumulating evidence suggests that long non-coding RNAs function as pivotal regulators in tumorigenesis and progression. However, their biological roles in breast cancer remain largely unknown. Here, we found that IGF2 antisense RNA (IGF2-AS) was significantly decreased in breast cancer tissues, cell lines, and plasma. Patients with low IGF2-AS were more likely to develop larger tumor size and later clinical stage. Overexpression of IGF2-AS evidently inhibited the proliferation and induced apoptosis of MCF-7 and T47D cells in vitro, as well as retarded tumor growth in vivo. Further investigation revealed that IGF2-AS inhibited the expression of its sense-cognate gene IGF2 in an epigenetic DNMT1-dependent manner, resulting in the inactivation of downstream oncogenic PI3K/AKT/mTOR signaling pathway. Enforced expression of IGF2 could significantly block the tumor inhibitory effect of IGF2-AS. Importantly, we found that IGF2-AS could be used as an effective biomarker for breast cancer diagnosis and prognosis. Taken together, our study indicates that IGF2-AS is a tumor suppressor in breast cancer, restoration of IGF2-AS may be a promising treatment for this fatal disease.

scholarly journals Quercetin Is a Flavonoid Breast Cancer Resistance Protein Inhibitor with an Impact on the Oral Pharmacokinetics of Sulfasalazine in Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 397
Author(s):  
Yoo-Kyung Song ◽  
Jin-Ha Yoon ◽  
Jong Kyu Woo ◽  
Ju-Hee Kang ◽  
Kyeong-Ryoon Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Fold Increase ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cancer Resistance ◽  
Concentration Dependent Manner ◽  
Resistance Protein

The potential inhibitory effect of quercetin, a major plant flavonol, on breast cancer resistance protein (BCRP) activity was investigated in this study. The presence of quercetin significantly increased the cellular accumulation and associated cytotoxicity of the BCRP substrate mitoxantrone in human cervical cancer cells (HeLa cells) in a concentration-dependent manner. The transcellular efflux of prazosin, a stereotypical BCRP substrate, was also significantly reduced in the presence of quercetin in a bidirectional transport assay using human BCRP-overexpressing cells; further kinetic analysis revealed IC50 and Ki values of 4.22 and 3.91 μM, respectively. Moreover, pretreatment with 10 mg/kg quercetin in rats led to a 1.8-fold and 1.5-fold increase in the AUC8h (i.e., 44.5 ± 11.8 min∙μg/mL vs. 25.7 ± 9.98 min∙μg/mL, p < 0.05) and Cmax (i.e., 179 ± 23.0 ng/mL vs. 122 ± 23.2 ng/mL, p < 0.05) of orally administered sulfasalazine, respectively. Collectively, these results provide evidence that quercetin acts as an in vivo as well as in vitro inhibitor of BCRP. Considering the high dietary intake of quercetin as well as its consumption as a dietary supplement, issuing a caution regarding its food–drug interactions should be considered.

scholarly journals A New Highlight of Ephedra alata Decne Properties as Potential Adjuvant in Combination with Cisplatin to Induce Cell Death of 4T1 Breast Cancer Cells In Vitro and In Vivo

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 362 ◽  
Author(s):  
Fairouz Sioud ◽  
Souheila Amor ◽  
Imène ben Toumia ◽  
Aida Lahmar ◽  
Virginie Aires ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Protective Action ◽  
Dependent Manner ◽  
4T1 Breast Cancer ◽  
Induced Apoptosis ◽  
Cellular Modifications

Despite major advances in the last 10 years, whether in terms of prevention or treatment, the 5 year survival rate remains relatively low for a large number of cancers. These therapeutic failures can be the consequence of several factors associated with the cellular modifications or with the host by itself, especially for some anticancer drugs such as cisplatin, which induces a nephrotoxicity. In the strategy of research for active molecules capable both of exerting a protective action against the deleterious effects of cisplatin and exerting a chemosensitizing action with regard to cancer cells, we tested the potential effects of Ephedra alata Decne extract (E.A.) rich in polyphenolic compounds towards a 4T1 breast cancer model in vitro and in vivo. We showed that E.A. extract inhibited cell viability of 4T1 breast cancer cells and induced apoptosis in a caspase-dependent manner, which involved intrinsic pathways. Very interestingly, we observed a synergic antiproliferative and pro-apoptotic action with cisplatin. These events were associated with a strong decrease of breast tumor growth in mice treated with an E.A./cisplatin combination and simultaneously with a decrease of hepato- and nephrotoxicities of cisplatin.

scholarly journals Periplocin Extracted from Cortex Periplocae Induced Apoptosis of Gastric Cancer Cells via the ERK1/2-EGR1 Pathway

2016 ◽  
Vol 38 (5) ◽  
pp. 1939-1951 ◽  
Author(s):  
Lei Li ◽  
Lian-Mei Zhao ◽  
Su-li Dai ◽  
Wen-Xuan Cui ◽  
Hui-Lai Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Induced Apoptosis

Background/Aims: Periplocin is extracted from the traditional herbal medicine cortex periplocae, which has been reported to suppress the growth of cancer cells. However, little is known about its effect on gastric cancer cells. Methods: Gastric cancer cells were treated with periplocin, and cell viability was assessed using MTS assay. Flow cytometry and TUNEL staining were performed to evaluate apoptosis, and protein expression was examined by western blotting. Microarray analysis was used to screen for changes in related genes. Results: We found that periplocin had an inhibitory effect on gastric cancer cell viability in a dose-dependent manner. Periplocin inhibited cell viability via the ERK1/2-EGR1 pathway to induce apoptosis. Periplocin also inhibited the growth of tumor xenografts and induced apoptosis in vivo. Conclusion: Our results show that periplocin inhibits the proliferation of gastric cancer cells and induces apoptosis in vitro and in vivo, indicating its potential to be used as an antitumor drug.

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

1996 ◽  
Vol 63 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Chun W. Wong ◽  
Geoffrey O. Regester ◽  
Geoffrey L. Francis ◽  
Dennis L. Watson
Keyword(s):  
Immune Responses ◽  
Bovine Milk ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Milk Whey ◽  
Significant Difference ◽  
Lymphocyte Phenotypes ◽  
Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

Aqueous extracts of avocado pear (Persea americana Mill.) leaves and seeds exhibit anti-cholinesterases and antioxidant activities in vitro

2016 ◽  
Vol 27 (2) ◽  
Author(s):  
Ganiyu Oboh ◽  
Veronica O. Odubanjo ◽  
Fatai Bello ◽  
Ayokunle O. Ademosun ◽  
Sunday I. Oyeleye ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Inhibitory Effect ◽  
Seed Extract ◽  
Persea Americana ◽  
Dependent Manner ◽  
Natural Treatment

AbstractAvocado pear (The inhibitory effects of extracts on AChE and BChE activities and antioxidant potentials (inhibition of FeThe extracts inhibited AChE and BChE activities and prooxidant-induced TBARS production in a dose-dependent manner, with the seed extract having the highest inhibitory effect and the leaf extract exhibiting higher phenolic content and radical scavenging abilities, but lower Fe chelation ability compared with that of the seed. The phytochemical screening revealed the presence of saponins, alkaloids, and terpenoids in both extracts, whereas the total alkaloid profile was higher in the seed extract than in the leaf extract, as revealed by GC-FID.The anti-cholinesterase and antioxidant activities of avocado leaf and seed could be linked to their phytoconstituents and might be the possible mechanisms underlying their use as a cheap and natural treatment/management of AD. However, these extracts should be further investigated in vivo.

scholarly journals Tenovin-6 impairs autophagy by inhibiting autophagic flux

2017 ◽  
Vol 8 (2) ◽  
pp. e2608-e2608 ◽  
Author(s):  
Hongfeng Yuan ◽  
Brandon Tan ◽  
Shou-Jiang Gao
Keyword(s):  
Cell Types ◽  
Inhibitory Effect ◽  
Lymphocytic Leukemia ◽  
Autophagic Flux ◽  
Dependent Manner ◽  
Autophagy Pathway ◽  
Sarcoma Cells ◽  
Regulatory Functions

Abstract Tenovin-6 has attracted significant interest because it activates p53 and inhibits sirtuins. It has anti-neoplastic effects on multiple hematopoietic malignancies and solid tumors in both in vitro and in vivo studies. Tenovin-6 was recently shown to impair the autophagy pathway in chronic lymphocytic leukemia cells and pediatric soft tissue sarcoma cells. However, whether tenovin-6 has a general inhibitory effect on autophagy and whether there is any involvement with SIRT1 and p53, both of which are regulators of the autophagy pathway, remain unclear. In this study, we have demonstrated that tenovin-6 increases microtubule-associated protein 1 light chain 3 (LC3-II) level in diverse cell types in a time- and dose-dependent manner. Mechanistically, the increase of LC3-II by tenovin-6 is caused by inhibition of the classical autophagy pathway via impairing lysosomal function without affecting the fusion between autophagosomes and lysosomes. Furthermore, we have revealed that tenovin-6 activation of p53 is cell type dependent, and tenovin-6 inhibition of autophagy is not dependent on its regulatory functions on p53 and SIRT1. Our results have shown that tenovin-6 is a potent autophagy inhibitor, and raised the precaution in interpreting results where tenovin-6 is used as an inhibitor of SIRT1.

scholarly journals HDAC6 inhibitor WT161 performs antitumor effect on osteosarcoma and synergistically interacts with 5-FU

2021 ◽  
Author(s):  
Jun Sun ◽  
Wei Wu ◽  
Xiaofeng Tang ◽  
Feifei Zhang ◽  
Cheng Ju ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Synergistic Inhibition ◽  
Proliferative Effect ◽  
Xenograft Models ◽  
Hdac6 Inhibitor ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Background: WT161, as a selective HDAC6 inhibitor, has been shown to play anti-tumor effects on several kinds of cancers. The aim of this study is to explore the roles of WT161 in osteosarcoma and its underlying mechanisms. Methods: The anti-proliferative effect of WT161 on osteosarcoma cells was examined using MTT assay and colony formation assay. Cell apoptosis was analyzed using flow cytometer. The synergistic effect was evaluated by isobologram analysis using CompuSyn software. The osteosarcoma xenograft models were established to evaluate the anti-proliferative effect of WT161 in vivo. Results: WT161 suppressed the cell growth and induced apoptosis of osteosarcoma cells in a dose- and time-dependent manner. Mechanistically, we found that WT161 treatment obviously increased the protein level of PTEN and decreased the phosphorylation level of AKT. More importantly, WT161 show synergistic inhibition with 5-FU on osteosarcoma cells in vitro and in vivo. Conclusions: These results indicate that WT161 inhibits the growth of osteosarcoma through PTEN and has a synergistic efficiency with 5-FU.

scholarly journals In vitro inhibitory effect of obtusofolin on the activity of CYP3A4, 2C9, and 2E1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Na Liu ◽  
Ping Chen ◽  
Xiaojun Du ◽  
Junxia Sun ◽  
Shasha Han
Keyword(s):  
Human Liver ◽  
Competitive Inhibition ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Inhibition Model ◽  
Dose Dependent

Abstract Background Obtusofolin is the major active ingredient of Catsia tora L., which possesses the activity of improving eyesight and protecting the optic nerve. Investigation on the interaction of obtusofolin with cytochrome P450 enzymes (CYP450s) could provide a reference for the clinical application of obtusofolin. Methods The effect of obtusofolin on the activity of CYP450s was investigated in the presence of 100 μM obtusofolin in pooled human liver microsomes (HLMs) and fitted with the Lineweaver–Burk plots to characterize the specific inhibition model and kinetic parameters. Results Obtusofolin was found to significantly inhibited the activity of CYP3A4, 2C9, and 2E1. In the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM obtusofolin, the inhibition of these CYP450s showed a dose-dependent manner with the IC50 values of 17.1 ± 0.25, 10.8 ± 0.13, and 15.5 ± 0.16 μM, respectively. The inhibition of CYP3A4 was best fitted with the non-competitive inhibition model with the Ki value of 8.82 μM. While the inhibition of CYP2C9 and 2E1 was competitive with the Ki values of 5.54 and 7.79 μM, respectively. After incubating for 0, 5, 10, 15, and 30 min, the inhibition of CYP3A4 was revealed to be time-dependent with the KI value of 4.87 μM− 1 and the Kinact value of 0.0515 min− 1. Conclusions The in vitro inhibitory effect of obtusofolin implying the potential drug-drug interaction between obtusofolin and corresponding substrates, which needs further in vivo validations.

IMB-BZ as an Inhibitor Targeting ESX-1 Secretion System to Control Mycobacterial Infection

2021 ◽  
Author(s):  
Pingping Jia ◽  
Yi Zhang ◽  
Jian Xu ◽  
Mei Zhu ◽  
Shize Peng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterial Infection ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
New Drugs ◽  
Dependent Manner ◽  
High Potency ◽  
Resistance Development

Abstract Background Resistance to anti-tuberculosis (TB) drug is a major issue in TB control, and demands the discovery of new drugs targeting virulence factor ESX-1. Methods We first established a high-throughput screen (HTS) assay for the discovery of ESX-1 secretion inhibitors. The positive hits were then evaluated for the potency of diminishing the survival of virulent mycobacterium and reducing bacterial virulence. We further investigated the probability of inducing drug-resistance and the underlying mechanism using M-PFC. Results A robust HTS assay was developed to identify small molecules that inhibit ESX-1 secretion without impairing bacterial growth in vitro. A hit named IMB-BZ specifically inhibits the secretion of CFP-10 and reduces virulence in an ESX-1-dependent manner, therefore resulting in significant reduction in intracellular and in vivo survival of mycobacteria. Blocking the CFP-10-EccCb1 interaction directly or indirectly underlies the inhibitory effect of IMB-BZ on the secretion of CFP-10. Importantly, our finding shows that the ESX-1 inhibitors pose low risk of drug resistance development by mycobacteria in vitro as compared with traditional anti-TB drug, and exhibit high potency against chronic mycobacterial infection. Conclusion Targeting ESX-1 may lead to the development of novel therapeutics for tuberculosis. IMB-BZ holds the potential for future development into a new anti-TB drug.

Effect of Auraptene on angiogenesis in Xenograft model of breast cancer

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mohammad Reza Shiran ◽  
Elham Mahmoudian ◽  
Abolghasem Ajami ◽  
Seyed Mostafa Hosseini ◽  
Ayjamal Khojasteh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Animal Model ◽  
Protein Expression ◽  
Western Blot ◽  
Xenograft Model ◽  
Dependent Manner ◽  
Concentration Dependent Manner

Abstract Objectives 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 in-vitro and in-vivo model of breast cancer. Methods In this study, 4T, MDA-MB-231 and HUVEC cell lines were used. The proliferation study was done by MTT assay. For tube formation assay, 250 matrigel, 1 × 104 HUVEC treated with Auraptene, 20 ng/mL EGF, 20 ng/mL bFGF and 20 ng/mL VEGF were used. Gene expression of important gene related to angiogenesis in animal model of breast cancer was investigated by Real-time PCR. Protein expression of VCAM-1 and TNFR-1 gene related to angiogenesis in animal model of breast cancer was investigated by western-blot. Results 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. Conclusions 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.

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