scholarly journals Effects of an azasterol inhibitor of sterol 24-transmethylation on sterol biosynthesis and growth of Leishmania donovani promastigotes

1995 ◽  
Vol 308 (1) ◽  
pp. 31-38 ◽  
Author(s):  
P A Haughan ◽  
M L Chance ◽  
L J Goad
Keyword(s):  
Cell Proliferation ◽  
Leishmania Donovani ◽  
Primary Site ◽  
Sterol Biosynthesis ◽  
Proliferation Inhibition ◽  
Complete Replacement ◽  
Inhibition Of Growth ◽  
Absolute Requirement ◽  
Cell Proliferation Inhibition ◽  
Site Of Action

Leishmania donovani promastigotes were cultured in the presence of an azasterol (20-piperidin-2-yl-5 alpha-pregnane-3 beta,20-diol) to determine the effects on sterol biosynthesis and cell proliferation. Inhibition of growth increased gradually with azasterol concentrations up to 5 micrograms/ml; concentrations of azasterol exceeding 5 micrograms/ml were lethal. Sterol biosynthesis was affected by the azasterol when administered at concentrations as low as 100 pg/ml. The primary site of action was the alkylation at C-24 of a delta 24-sterol precursor. The 24-alkylated sterols [ergosta-5,7,24(24(1))-trien-3 beta-ol and ergosta-5,7,22-trien-3 beta-ol] of the protozoan were replaced by delta 24-cholesta-type sterols which then accumulated in the cells. Administration of the azasterol together with a bis-triazole inhibitor of the 14 alpha-methylsterol 14-demethylase reaction, which operates in sterol biosynthesis, resulted in depletion of 24-alkylsterols and their replacement with predominantly 14 alpha-methylsterols lacking a 24-alkyl group. Continuous subculture of promastigotes in the presence of the azasterol resulted in gradual depletion of 24-alkylsterols and their complete replacement by delta 24-cholesta-type sterols. Transfer of the azasterol-treated cells to medium lacking azasterol resulted in a gradual restoration, after several subcultures, of the normal 24-alkylsterol pattern. The results indicate that, although 24-alkylsterols are normally produced by the protozoan, it can nevertheless survive with sterols possessing only the cholestane skeleton. Thus there is no absolute requirement for 24-alkylsterols to fulfil some essential ‘sparking’ role associated with cell growth in promastigotes.

scholarly journals Upregulation of miRNA-23a-3p rescues high glucose-induced cell apoptosis and proliferation inhibition in cardiomyocytes

2020 ◽  
Vol 56 (10) ◽  
pp. 866-877
Author(s):  
Fang Wu ◽  
Feng Wang ◽  
Qian Yang ◽  
Yawen Zhang ◽  
Ke Cai ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Myocardial Injury ◽  
Proliferation Inhibition ◽  
Cardiomyocyte Proliferation ◽  
Injury Model ◽  
Cell Proliferation Inhibition ◽  
Glucose Treatment

AbstractMaternal hyperglycemia potentially inhibits the development of the fetal heart by suppressing cardiomyocyte proliferation and promoting apoptosis. Different studies have indicated that miRNAs are key regulators of cardiomyocyte proliferation, differentiation, and apoptosis and play a protective role in a variety of cardiovascular diseases. However, the biological function of miRNA-23a in hyperglycemia-related cardiomyocyte injury is not fully understood. The present study investigated the effect of miRNA-23a-3p on cell proliferation and apoptosis in a myocardial injury model induced by high glucose. H9c2 cardiomyocytes were exposed to high glucose to establish an in vitro myocardial injury model and then transfected with miRNA-23a-3p mimics. After miRNA-23a-3p transfection, lens-free microscopy was used to dynamically monitor cell numbers and confluence and calculate the cell cycle duration. CCK-8 and EdU incorporation assays were performed to detect cell proliferation. Flow cytometry was used to measured cell apoptosis. Upregulation of miRNA-23a-3p significantly alleviated high glucose-induced cell apoptosis and cell proliferation inhibition (p < 0.01 and p < 0.0001, respectively). The cell cycle of the miRNA-23a-3p mimics group was significantly shorter than that of the negative control group (p < 0.01). The expression of cell cycle–activating and apoptosis inhibition-associated factors Ccna2, Ccne1, and Bcl-2 was downregulated by high glucose and upregulated by miRNA-23a-3p overexpression in high glucose-injured H9c2 cells. miRNA-23a-3p mimics transfection before high glucose treatment had a significantly greater benefit than transfection after high glucose treatment (p < 0.0001), and the rescue effect of miRNA-23a-3p increased as the concentration increased. This study suggests that miRNA-23a-3p exerted a dose- and time-dependent protective effect on high glucose-induced H9c2 cardiomyocyte injury.

scholarly journals PTP4A3, A Novel Target Gene of HIF-1alpha, Participates in Benzene-Induced Cell Proliferation Inhibition and Apoptosis through PI3K/AKT Pathway

2020 ◽  
Vol 17 (3) ◽  
pp. 910
Author(s):  
Yunqiu Pu ◽  
Fengxia Sun ◽  
Rongli Sun ◽  
Zhaodi Man ◽  
Shuangbin Ji ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Target Gene ◽  
Akt Pathway ◽  
Proliferation Inhibition ◽  
Cell Proliferation Inhibition ◽  
A Cell ◽  
Novel Target ◽  
In Cells

Benzene, a commonly used chemical, has been confirmed to specifically affect the hematopoietic system as well as overall human health. PTP4A3 is overexpressed in leukemia cells and is related to cell proliferation. We previously found that HIF-1alpha was involved in benzene toxicity and PTP4A3 may be the target gene of HIF-1alpha via ChIP-seq. The aim of this study is to confirm the relationship between HIF-1alpha and PTP4A3 in benzene toxicity, as well as the function of PTP4A3 on cell toxicity induced by 1,4-benzoquinone (1,4-BQ). Our results indicate that HIF-1alpha could regulate PTP4A3 with in vivo and in vitro experiments. A cell line with suppressed PTP4A3 was established to investigate the function of PTP4A3 in 1,4-BQ toxicity in vitro. The results revealed that cell proliferation inhibition was more aggravated in PTP4A3 low-expression cells than in the control cells after 1,4-BQ treatment. The relative oxygen species (ROS) significantly increased in cells with inhibited PTP4A3, while the rise was inferior to the control cells at the 20 μM 1,4-BQ group. An increase in DNA damage was seen in PTP4A3 down-regulated cells at the 10 μM 1,4-BQ group, whereas the results reversed at the concentration of 20 μM. Moreover, the apoptosis rate increased higher in down-regulated PTP4A3 cells after 1,4-BQ exposure. In addition, PI3K/AKT pathway was significantly restrained in cells with inhibited PTP4A3 after 1,4-BQ treatment. Our results indicate that HIF-1alpha may regulate PTP4A3 to be involved in benzene toxicity. Inhibition of PTP4A3 could aggravate cell proliferation suppression and apoptosis by regulating PI3K/AKT pathway after 1,4-BQ treatment.

Knockdown of long noncoding RNA FGFR3- AS1 induces cell proliferation inhibition, apoptosis and motility reduction in bladder cancer

2018 ◽  
Vol 21 (2) ◽  
pp. 277-285 ◽  
Author(s):  
Xinhui Liao ◽  
Jieqing Chen ◽  
Yuchen Liu ◽  
Anbang He ◽  
Jianting Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Proliferation Inhibition ◽  
Cell Proliferation Inhibition

An Overview on Genistein and its Various Formulations

Drug Research ◽  
2018 ◽  
Vol 69 (06) ◽  
pp. 305-313 ◽  
Author(s):  
Neha Jaiswal ◽  
Juber Akhtar ◽  
Satya Prakash Singh ◽  
Farogh Ahsan ◽  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Lower Risk ◽  
Ayurvedic Medicine ◽  
Pharmacological Properties ◽  
Proliferation Inhibition ◽  
Cell Proliferation Inhibition

AbstractGenistein is the natural isoflavone and a phytoestrogen with a broad range of pharmacological properties, such as tyrosine and topoisomerase inhibition. It also induces apoptosis and cell proliferation inhibition, differentiates cancer cells. Added health benefits include the reduction of osteoporosis by suppressing osteoclasts and lymphocyte functions, decreased the risk of cardiovascular attacks and relieved postmenopausal problems. Genistein traditionally used in Chinese and Ayurvedic medicine and are found to be associated with lower risk of breast, prostate and lung cancer. Numerous factors comprising genetic, epigenetic and transcriptomic alterations are evidenced to be responsible for breast, prostate and lung cancer. In present review, an overview on genistein, the various analytical methods and drug delivery approaches to determine genistein in the formulations are discussed. It may help to develop novel formulations with better solubility and bioavailability of genistein. The tumor cell scan may be targeted to form a stable genistein formulation.

Anti-Cancer Effects of Rapamycin on U937 Cell Line.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4518-4518
Author(s):  
Lina Jin ◽  
Chenchen Fu ◽  
Jiannong Cen ◽  
Peishuai Chen ◽  
De Pei Wu
Keyword(s):  
Cell Proliferation ◽  
Cell Line ◽  
U937 Cell ◽  
S Phase ◽  
G1 Phase ◽  
Proliferation Inhibition ◽  
Inhibition Rate ◽  
Phosphorylation Level ◽  
Cell Proliferation Inhibition ◽  
Anti Cancer

Abstract Purpose: Cytotoxicity of rapamycin alone or in combination with arsenic trioxide in lymphoma cell line U937 was assessed, for the study of Anti-cancer effects of rapamycin. Methods: cell vability and proliferation was analyzed by MTT and cell counting, clone formulating ability was analyzed by semisolid medium, cell cycle was analyzed by Propidium Iodide/RN-ase stain, the phosphorylation level of mammalian target of rapamycin (mTOR) was detected after marked by Phospho-mTOR antibody (Ser2448) and FITC. Expression of P27 was assessed by western- blot. Result: 1.MTT measurement showed with increasing concentrations of RAPA (10 nM 100 nM, 1000 nM) cell proliferation inhibition rate was follwed 16.2%, 25.5%, 47.8%. Clonogenic assay showed the U937 proliferation inhibition rate was 80.5% in a 7-day leukemia colony-forming assay with concentration of 10 nM RAPA.2 RAPA 10nM, As2O3 0.6uM, As2O3 0.9uM alone, RAPA 10nM in combination with As2O3 0.6uM and 0.9uM, cell proliferation inhibition rate was followed 13%, 26%, 35%, 43%, 54%. 3. Propidium Iodide/RN-ase measurement showed RAPA resulted in U937 cell arrested in G1-phase, and was blocked in S-phase. 4. FCM showed the phosphorylation level of mTOR down-regulated significantly after treated by rapamycin (10 nM),5.The expression of P27 enhanced after treatd by rapamycin (10 nM) Conclutions: From the experiment we can see rapamycin alone can inhibit the proliferation and clone formulating ability of U937 cell line. mTOR kinase is involved in the regulation of cell growth and proliferation. Rapamycin can down-regulate the phosphorylation level of mTOR, which can induce increasing expression of P27, As a result U937 arrest in G1-phase and block in S-phase. Interestingly rapamycin exert additive effect in proliferation experiment when combind with As2O3, higher than rapamycin or As2O3 alone.

scholarly journals β1 integrin-mediated multicellular resistance in hepatocellular carcinoma through activation of the FAK/Akt pathway

2018 ◽  
Vol 46 (4) ◽  
pp. 1311-1325 ◽  
Author(s):  
Tao Tian ◽  
Chun-Li Li ◽  
Xiao Fu ◽  
Shu-Hong Wang ◽  
Jun Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Akt Pathway ◽  
Β1 Integrin ◽  
Proliferation Inhibition ◽  
Multicellular Spheroids ◽  
Inhibitory Antibody ◽  
Cell Proliferation Inhibition

Objective To explore the role and mechanism of β1 integrin in the regulation of multicellular drug resistance in hepatocellular carcinoma (HCC). Methods This in vitro study used a liquid overlay technique to obtain multicellular spheroids of two human HCC cell lines, HepG2 and Bel-7402. The morphology of the spheroids was observed by optical and electron microscopy. The effects of exposure to 5-fluorouracil (5-FU) and cisplatin (CDDP) on cell proliferation and the induction of apoptosis were assessed in monolayer cells and multicellular spheroids. The levels of β1 integrin and the effects on the focal adhesion kinase (FAK)/protein kinase B (Akt) pathway were evaluated using Western blot analysis, immunofluorescence and flow cytometry. The role of β1 integrin was confirmed by using an inhibitory antibody. Results Cell proliferation inhibition and cell apoptosis induced by 5-FUl and CDDP were abrogated in multicellular spheroids compared with monolayer cells. There were high levels of β1 integrin in multicellular spheroids. β1 integrin inhibitory antibody prevented the formation of multicellular spheroids, coupled with a significant increase in proliferation inhibition and apoptosis induction. β1 integrin inhibitory antibody effectively suppressed activation of both FAK and Akt in multicellular spheroids. Conclusions β1 integrin mediated multicellular drug resistance through the FAK/Akt pathway in HCC spheroids.

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