Abstract：
:Novel therapeutic strategies are needed to address and to solve the emerging problem of hypoxia-induced resistance to anticancer drugs. N-(4-Hydroxyphenyl)retinamide (4-HPR) exhibits potent anticancer and chemopreventive activities, but its inefficiency under hypoxia, through undetermined mechanisms, may contribute to its lack of activity in clinical trials. In this study, we showed that under normoxia, 4-HPR resulted in apoptosis and ultimate cell death; in contrast, under hypoxia, autophagy was preferentially induced by 4-HPR at an equivalent concentration, accompanied by microtubule associated protein light-chain 3 (LC3) conversion and acidic vesicular organelle formation. Under hypoxia, autophagy inhibition by 3-methyladenine or chloroquine significantly enhanced apoptosis and decreased cell viability in 4-HPR-exposed cells, indicating that autophagy prevents cancer cell death and presumably leads to hypoxia-induced resistance to 4-HPR. Importantly, knockdown of hypoxia-inducible factor-1α (HIF-1α) inhibited autophagy but promoted 4-HPR-induced apoptosis under hypoxia, demonstrating its critical role as a mediator of this protective autophagy. The present study provides the first evidence supporting the hypothesis that autophagy and apoptosis can be differentially induced by 4-HPR under different oxygen conditions; mediated by HIF-1α, 4-HPR-induced autophagy under hypoxia confers a survival advantage to HeLa cells, protects them from 4-HPR-induced death signals, and thus contributes to their hypoxia-induced resistance to this agent. Our data suggest that autophagy inhibition is a potential alternative strategy to overcome hypoxia-induced resistance to 4-HPR and enhance the anticancer activities of this agent.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Liu XW,Su Y,Zhu H,Cao J,Ding WJ,Zhao YC,He QJ,Yang Bdoi
10.1016/j.phrs.2010.07.002subject
Has Abstractpub_date
2010-11-01 00:00:00pages
416-25issue
5eissn
1043-6618issn
1096-1186pii
S1043-6618(10)00142-8journal_volume
62pub_type
杂志文章abstract：:Pharmacokinetics is a relatively young branch of the life sciences, which has developed rapidly in the last 15-20 years, thanks to a series of analytical achievements that have allowed drug concentrations to be measured in biological matrices with highly selective and sensitive methods. Most old drugs and all new drug...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1006/phrs.1997.0254
更新日期：1997-12-01 00:00:00
abstract：:The renal and metabolic effects of chronic carnitine administration were evaluated in the early stages of experimentally-induced renal failure. Laevo-carnitine (n = 5), Propionyl-carnitine (n = 5) both at 200 mg kg-1 of body weight, or vehicle (physiological saline solution, 0.4 ml kg-1 body weight, n = 5) were admini...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1996.0083
更新日期：1996-09-01 00:00:00
abstract：:The effects of the P(2)-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl- 2('),4(')- disulphonic acid (PPADS), the nitric oxide (NO) synthase inhibitor N(G)-nitro- l -arginine (l -NOARG), the K(+)-channel blocker apamin, the pituitary adenylate cyclase activating peptide (PACAP) antagonist PACAP(6-38) and the s...
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doi：10.1006/phrs.2000.0742
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abstract：:In the present study, hyperglycaemia was induced by intraperitoneal injection of streptozotocin (65 mg/kg). Treatment with glibenclamide (GB) in a dose of 0.45 or 0.9 mg/kg significantly decreased plasma glucose level in a dose-related manner. Administration of nadolol (ND) in a dose of 5 or 10 mg/kg did not affect pl...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1996.0057
更新日期：1996-07-01 00:00:00
abstract：:Mammalian cells are commonly employed in screening assays to identify active compounds that could potentially affect the progression of different human diseases including retinitis pigmentosa (RP), a class of inherited diseases causing retinal degeneration with compromised vision. Using transcriptome analysis, we comp...
journal_title：Pharmacological research
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doi：10.1016/j.phrs.2016.10.031
更新日期：2017-01-01 00:00:00
abstract：:The review emphasizes the role of NGF, the most representative member of the neurotrophins family, in cardiac physiopathology with a particular focus on healing and sprouting processes occurring after tissue damage. Cardiac and circulating NGF levels dramatically increase following myocardial injury (MI). A very early...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
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journal_title：Pharmacological research
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doi：10.1006/phrs.1997.0225
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abstract：:Posttranslational modifications of proteins are important regulatory processes endowing the proteins functional complexity. Over the last decade, numerous studies have shed light on the roles of palmitoylation, one of the most common lipid modifications, in various aspects of neuronal functions. Major players regulati...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
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更新日期：2016-09-01 00:00:00
abstract：:An interaction of drug with food, herbs, and dietary supplements is usually the consequence of a physical, chemical or physiologic relationship between a drug and a product consumed as food, nutritional supplement or over-the-counter medicinal plant. The current educational review aims at reminding to the prescribing ...
journal_title：Pharmacological research
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更新日期：2017-04-01 00:00:00
abstract：:Heart rate recovery at 1min (HRR1) is a strong predictor of all-cause mortality. The effects of statins on the autonomic nervous system may account for their beneficial effects in survival. Our aim was to determine if statin therapy improves heart rate recovery in hypercholesterolemic patients with type 2 diabetes mel...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2006.09.002
更新日期：2006-12-01 00:00:00
abstract：:Radiotherapy plays a critical role in the treatment of non-small cell lung cancer (NSCLC). However, radioresistance is a major barrier against increasing the efficiency of radiotherapy for NSCLC. To understand the mechanisms underlying NSCLC radioresistance, we previously focused on the potential involvement of PIM1, ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2013.01.005
更新日期：2013-04-01 00:00:00
abstract：:Efficacy and safety assessments are essential thresholds for drug candidates from preclinical to clinical research. Conventional mammalian in vivo models cannot offer rapid pharmacological and toxicological screening, whereas cell-based or cell-free in vitro systems often lead to inaccurate results because of the lack...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2018.04.011
更新日期：2018-07-01 00:00:00
abstract：:Boldo (Peumus boldus Mol.), a Chilean tree traditionally employed in folk medicine and recognized as a herbal remedy in a number of pharmacopoeias, mainly for the treatment of liver ailments, has recently been the subject of increasing attention. Boldine, in particular, the major and most characteristic alkaloidal con...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/1043-6618(94)80093-6
更新日期：1994-01-01 00:00:00
abstract：:It has been suggested that hypertension results from a loss of immunological tolerance and the resulting autoimmunity may be an important underlying factor of its pathogenesis. This stems from the observations that many of the features involved in autoimmunity are also implicated in hypertension. Furthermore, the unde...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.09.008
更新日期：2016-11-01 00:00:00
abstract：:The pharmacokinetics of doxycycline hydrochloride (DoxHcl) at a dose of 5 mg kg-1 BW was studied after an intravenous (i.v.) bolus and intramuscular (i.m.) injections in non lactating goats. A microbiological assay employing Bacillus subtilis as the test organism was used to measure its concentrations in serum and uri...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2003.10.012
更新日期：2004-05-01 00:00:00
abstract：:Monoclonal antibodies (mAb) have revolutionised the way in which we treat disease. From cancer to autoimmunity, antibody therapy has been responsible for some of the most impressive clinical responses observed in the last 2 decades. A key component of this success has been their generally low levels of toxicity, and u...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2015.07.003
更新日期：2015-09-01 00:00:00
abstract：:In incubated blood mononuclear cells from normal subjects bezafibrate inhibited the incorporation of 14C-acetate into squalene, methylsterols and cholesterol. Similarly, the drug produced a sharp decrease of the incorporation of labelled 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) into non-saponifiable lipids, whi...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(89)80002-7
更新日期：1989-05-01 00:00:00
abstract：:The neurohormonal factor arginine vasopressin (AVP) produces potent systemic vasoconstriction as well as water retention in the kidneys via the V(1a) and V(2) receptors, respectively. Therefore, AVP may be considered as an aggravating factor of cardiac failure. In the present study, the effects of intravenous (i.v.) i...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043661802002062
更新日期：2002-11-01 00:00:00
abstract：:In previous studies we observed an enhanced anti-inflammatory activity of MPEG-SOD derivatives in acute inflammation in rat. To assess the activity in chronic inflammation we tested the compound with longer half-life (MPEG-SOD 18) in complete adjuvant arthritis in rat. According to the prophylactic schedule of treatme...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(05)80106-9
更新日期：1991-01-01 00:00:00
abstract：:The perioperative period is supposed to be a vulnerable period for cancer progression. Results of clinical studies indicate that the use of regional anesthesia can influence and improve oncological outcome of cancer patients. Uncontrolled cell proliferation and resistance to apoptotic cell death are important characte...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2015.03.017
更新日期：2015-05-01 00:00:00
abstract：:The effect of different L-histidine concentrations on human mammary tumour cell (CG5) proliferation was studied to test the hypothesis of a role of histidine in modulating sex steroid-regulated cell proliferation. Cell growth was only possible in the 10(-5) M and 10(-2) M range, while its inhibition by medroxyprogeste...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1996.0126
更新日期：1997-02-01 00:00:00
abstract：:The protective effect of L-carnitine or coenzyme Q10 (CoQ10) against high magnetic field (20 mT) induced testicular toxicity in mice were evaluated. Animals were injected with L-carnitine (200 mg kg(-1), i.p.) or CoQ10 (200 mg kg(-1), p.o.) 1h before exposure to fractionated doses (30 min per day, three times per week...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043661802001718
更新日期：2002-10-01 00:00:00
abstract：:The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by i...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2011.08.003
更新日期：2012-01-01 00:00:00
abstract：:The herbal formulation Sinpo-Tang (SPT) has long been used for various allergic diseases. We investigated the effect of SPT on the mast cell-mediated anaphylactic reactions in vivo and in vitro murine models. SPT dose dependently inhibited compound 48/80-induced ear swelling response and histamine release. SPT (0.001-...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043661802002037
更新日期：2002-11-01 00:00:00
abstract：:We aimed to investigate the cardiac changes in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with trastuzumab in an adjuvant setting. Two hundred and fifty-three women with HER2-positive breast cancer were included. The assessment of cardiovascular system and echocardiogr...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2013.10.001
更新日期：2013-12-01 00:00:00
abstract：:By the use of combined radioreceptor binding and autoradiographic techniques we attempted to analyse the biochemical characteristics and the anatomical localization of GABA-B receptors in sections of rat circle of Willis and pialarachnoid arteries. 3H-GABA in the presence of 40 microM isoguvacine and 2.5 mM CaCl2 was ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/1043-6618(90)90731-r
更新日期：1990-05-01 00:00:00
abstract：:A major focus of contemporary drug screening strategies is the identification of novel anticancer compounds, which often results in underutilization of resources. Current drug evaluation involves in vivo tumor (xenograft) regression as proof-of-principle for cytotoxicity (POC). However, this end-point lacks any assess...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.07.018
更新日期：2016-09-01 00:00:00
abstract：:Alzheimer's is the neurodegenerative disease affecting the largest number of patients in the world. In spite of the intense research of the last decades, progress about its knowledge and therapy was limited. In particular, various cytotoxic processes remained debated, while the few drugs approved for therapy were of o...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104316
更新日期：2019-08-01 00:00:00
abstract：BACKGROUND:Overexpression of heat shock proteins (Hsps) is associated to myocardial protection and it has been suggested that they could be a marker of cardiac preservation in conditions such as extracorporeal circulation. Aim of this study was to evaluate if cardioplegic arrest can modify the expression of Hsps in the...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(03)00193-2
更新日期：2003-11-01 00:00:00
abstract：:Using cultured human keratinocytes, the present study investigates the role of nitric oxide (NO) in the mediation of the antiproliferative effects of ultraviolet light A (UVA). UVA treatment of cells (3-21 J cm (-2)) caused a time- and dose-dependent increase in nitrite formation in a micromolar range. This effect was...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2001.0939
更新日期：2002-03-01 00:00:00
