Abstract：
:The mechanism underlying the resistance of cancer cells to chemotherapeutic drug varies with different cancer cells. Recent evidence shows that lysosomal function is associated with drug resistance of cancer cells. Artesunate, a derivative of artemisinin, displays broad antitumor activity and direct cytotoxicity on various tumor cells. Our previous study shows that artesunate increases autophagosome accumulation, while significantly decreases autolysosome number in cancer cells, suggesting that artesunate might impair the lysosomal function. In this study, we investigated the effects of artesunate on lysosomal function and its relationship with chemotherapeutic drug resistance in cancer cells. We found that the lysosomal function was significantly enhanced in two drug-resistant (A549/TAX and A549/DDP) cells. Furthermore, we showed that the enhanced lysosomal function by overexpression of transcription factor EB (TFEB) significantly increased MCF-7 cells resistance to doxorubicin (DOX), whereas the decreased lysosomal function by TFEB-knockdown or lysosome inhibitor chloroquine increased MCF-7 cells sensitivity to DOX. Treatment of A549/TAX cells with artesunate (2.5-50 μM) dose-dependently inhibited lysosomal function and the clearance of dysfunctional mitochondria, and induced cell apoptosis. Moreover, we demonstrated that artesunate exerted more potent inhibition on the resistant (A549/TAX and MCF-7/ADR) cells with higher activity of lysosomal function. Our results suggest that artesunate or other inhibitors of lysosomal function would be potential in the treatment of cancer cells with drug resistance caused by the enhanced lysosomal function.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Li Z,Zhu YT,Xiang M,Qiu JL,Luo SQ,Lin Fdoi
10.1038/s41401-020-0445-zsubject
Has Abstractpub_date
2020-07-23 00:00:00eissn
1671-4083issn
1745-7254pii
10.1038/s41401-020-0445-zpub_type
杂志文章abstract：:Volatile anesthetics improve postischemic cardiac function and reduce infarction even when administered for only a brief time at the onset of reperfusion. A recent study showed that sevoflurane postconditioning (SPC) attenuated myocardial reperfusion injury, but the underlying mechanisms remain unclear. In this study,...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-018-0066-y
更新日期：2019-01-01 00:00:00
abstract：AIM:To elucidate inhibition of protein kinase C alpha (PKC alpha) activity by staurosporine on apoptosis of oral cancer cell line tongue squamous cell carcinoma (TSCCa) cells and to clarify the role of survivin and caspase-3 in mediating apoptosis. METHODS:TSCCa cell viability was measured by MTT assay after 100 nmol/...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2005.00205.x
更新日期：2005-11-01 00:00:00
abstract：:In an effort to develop effective alternative strategies that increase the therapeutic efficacy and minimize the systemic toxicity of chemotherapeutic agents, more efforts are being directed towards the investigation of dietary supplements and other phytotherapeutic agents for their synergistic efficacy in combination...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1111/j.1745-7254.2007.00691.x
更新日期：2007-09-01 00:00:00
abstract：AIM:To investigate the effect of 7-hydroxystaurosporine (UCN-01), a selective protein kinase C (PKC) inhibitor, on cell growth, migration, and invasion in invasive human glioblastoma U-87MG cells. METHODS:PKC activity was determined based on the PKC-catalyzed transfer of the (32)P-phosphate group from [g-(32)P]ATP int...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2005.00087.x
更新日期：2005-04-01 00:00:00
abstract：AIM:To investigate possible intracellular signal molecules involved in diphenylhydantoin (DPH)-mediated apoptosis of cerebellar granule neurons (CGN) and explore possible molecular mechanisms of neurotoxicity of DPH. METHODS:Fluorescein diacetate (FDA) stain, hochest 33258 stain, and agar gel electrophoresis were used...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2003-06-01 00:00:00
abstract：AIM:Hydrogen peroxide (H2O2) is produced during liver transplantation. Ischemia/reperfusion induces oxidation and causes intracellular Ca2+ overload, which harms liver cells. Our goal was to determine the precise mechanisms of these processes. METHODS:Hepatocytes were extracted from rats. Intracellular Ca2+ concentrat...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2008.4
更新日期：2009-01-01 00:00:00
abstract：AIM:To investigate the protection of pulmonary arterial rings and cardiac myocytes of rats by raisanberine (RS), a derivative of berberine, against hypoxia injury and to elucidate the action mechanisms. METHODS:Adult SD rats were exposed to intermittent hypoxia for 17 d or 28 d. The pulmonary arterial rings were isola...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2012.7
更新日期：2012-05-01 00:00:00
abstract：:Lactoferrin (Lf) is an iron-binding glycoprotein of the transferrin family, which is expressed in most biological fluids with particularly high levels in mammalian milk. Its multiple activities lie in its capacity to bind iron and to interact with the molecular and cellular components of hosts and pathogens. Lf can bi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2013.200
更新日期：2014-05-01 00:00:00
abstract：AIM:Probucol, an anti-hyperlipidemic drug, has been reported to exert antitumor activities at various stages of tumor initiation, promotion and progression. In this study we examined whether the drug affected glioma cell growth in vitro and the underlying mechanisms. METHODS:Human glioma U87 and glioblastoma SF295 cel...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,收录出版
doi：10.1038/aps.2014.88
更新日期：2014-12-01 00:00:00
abstract：AIM:To differentiate the electrophysiological characteristics of somatic action potentials (AP) from isolated Neo and Juv nodose sensory neurons (NSN) and those from slices of intact Juv and adult rat nodose ganglia. METHODS:For isolated cell recordings nodose ganglia from 3-8 d old Neo and 4 weeks old Juv rats were d...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-06-01 00:00:00
abstract：AIM:In order to elucidate the molecular mechanism underlying the cardioprotection afforded by schisandrin B (Sch B), the effect of Sch B treatment on the sensitivity of mitochondria to Ca2+-stimulated permeability transition (PT) was investigated in rat hearts under normal and ischemia-reperfusion (I-R) conditions. RE...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00614.x
更新日期：2007-10-01 00:00:00
abstract：AIM:High mobility group box protein 1 (HMGB1) and receptor for the advanced glycation end product (RAGE) play pivotal roles in vascular inflammation and atherosclerosis. The aim of this study was to determine whether the HMGB1-RAGE axis was involved in the actions of simvastatin on vascular inflammation and atheroscler...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2013.8
更新日期：2013-06-01 00:00:00
abstract：AIM:Endothelium-dependent relaxations to certain neurohumoral substances are mediated by pertussis toxin-sensitive Gi/o protein. Our experiments were designed to determine the role, if any, of pertussis toxin-sensitive G-proteins in relaxations attributed to endothelium-derived hyperpolarizing factor (EDHF). METHODS:P...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00905.x
更新日期：2008-12-01 00:00:00
abstract：AIM:To present the 4 to 9 years (median: 6 years) treatment follow up of 10 HIV1-AIDS patients, 9 at AIDS and 1 at A3 stages. METHODS:We have applied from 1992 to 1994, AZT combined with 2 integrase inhibitors, acriflavine and hydroxy-methyl-ellipticine. We could shift, in 1994, to combinations of 3 drugs including tw...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-01-01 00:00:00
abstract：AIM:To determine whether ATP-sensitive potassium channels are altered in VSMC from arotas and mesenteric arteries of obese rat, and their association with obesity-triggered increase in blood pressure. METHODS:Obesity was induced by 24 weeks of high-fat diet feeding in male Sprague-Dawley rats. Control rats were fed wi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00810.x
更新日期：2008-10-01 00:00:00
abstract：AIM:G protein-coupled inwardly rectifying potassium channels (GIRK) are important for neuronal signaling and membrane excitability. In the present study, we intend to find whether GIRK channels express functionally in adult rat dorsal root ganglion (DRG) neurons. METHODS:We used RT-PCR to detect mRNA for 4 subunits of...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00478.x
更新日期：2007-02-01 00:00:00
abstract：AIM:Filamin binding LIM protein 1, also known as migfilin, is a skeleton organization protein that binds to mitogen-inducible gene 2 at cell-extracellular matrix adhesions. The aim of this study was to investigate the role of migfilin in cisplatin-induced apoptosis in human glioma cells, to determine the functional dom...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2012.123
更新日期：2012-10-01 00:00:00
abstract：:In this brief review we summarize the current fndings relative to the discovery of a small peptide ligand, phoenixin (PNX). Using a bioinformatic approach, two novel peptides PNX-14 and PNX-20 containing 14 and 20 amino acids, respectively, were isolated from diverse tissues including the brain, heart, lung and stomac...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2017.195
更新日期：2018-05-01 00:00:00
abstract：:Type capital I, Ukrainian natural killer T cells (NKT cells), a subset of CD1d-restricted T cells with invariant Valphabeta TCR, are characterized by prompt production of large amounts of Th1 and/or Th2 cytokines upon primary stimulation through the TCR complex. The rapid release of cytokines implies that type capital...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2010.119
更新日期：2010-09-01 00:00:00
abstract：AIM:To investigate the effects of diosgenin (Dio), a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves' disease (GD) and the underlying mechanisms. METHODS:Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were tre...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2013.133
更新日期：2014-01-01 00:00:00
abstract：AIM:To investigate the effects of onychin on the proliferation of cultured rat artery vascular smooth muscle cells (VSMCs) in the presence of 10% new-born calf serum (NCS). METHODS:Rat VSMCs were incubated with onychin 150 micromol/L or genistein 10 micromol/L in the presence of 10% NCS for 24 h. The proliferation of ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2005.00526.x
更新日期：2005-02-01 00:00:00
abstract：:An increasing number of cases of herb-induced liver injury (HILI) have been reported, presenting new clinical challenges. In this study, taking Polygonum multiflorum Thunb (PmT) as an example, we proposed a computational systems toxicology approach to explore the molecular mechanisms of HILI. First, the chemical compo...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2016.147
更新日期：2017-05-01 00:00:00
abstract：AIM:Seipin is a protein that resides in endoplasmic reticulum, and involved in both lipid metabolic disorders and motor neuropathy. The aim of this study was to investigate the effects of mutant seipin on autophagy system and the morphology of lipid droplets in vitro. METHODS:HEK-293, H1299 and MES23.5 cells were tran...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2014.164
更新日期：2015-04-01 00:00:00
abstract：AIM:To investigate whether geniposide, an iridoid glucoside extracted from gardenia jasminoides ellis fruits, inhibits cell adhesion to human umbilical vein endothelial cells (HUVECs) induced by high glucose and its underlying mechanisms. METHODS:HUVECs were isolated from human umbilical cords and cultured. The adhesi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2010.83
更新日期：2010-08-01 00:00:00
abstract：:Tobacco use is estimated to be the largest single cause of premature death in the world. Nicotine is the major addictive substance in tobacco products. After cigarette smoking, nicotine quickly acts on its target, nicotinic acetylcholine receptors (nAChRs), which are widely distributed throughout the mammalian central...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2010.137
更新日期：2010-09-01 00:00:00
abstract：:In drug design and discovery, binding affinity and selectivity are two basic properties of a drug candidate. Opioid receptors (ORs) are the main targets of strong analgesics. Like some other class A members of G-protein-coupled receptors (GPCRs), ORs exhibit complex selectivity on their ligands. The diversity of bindi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2017.132
更新日期：2018-03-01 00:00:00
abstract：AIM:To evaluate the pharmacokinetic characteristics of L-valyl-ara-C, a peptidomimetic prodrug of ara-C. METHODS:After the synthesis of L-valyl-ara-C, the in vitro stability of L-valyl-ara-C was examined in various biological media. Plasma pharmacokinetic profiles of ara-C and L-valyl-ara-C were also evaluated in rats...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00474.x
更新日期：2007-02-01 00:00:00
abstract：:Aspirin (ASA) is a cardioprotective drug with anti-cardiac fibrosis action in vivo. This study was aimed to clarify the anti-cardiac fibrosis action of ASA and the underlying mechanisms. Two heart injury models (injection of isoproterenol and ligation of the left anterior descending branch) were used in mice to induce...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2016.143
更新日期：2017-04-01 00:00:00
abstract：AIM:To evaluate retrospectively the association of cytochrome P450 3A (CYP3A) and ATP-binding cassette sub-family B member 1 (ABCB1) gene polymorphisms with the pharmacokinetics of cyclosporine A (CsA) in Chinese renal transplant patients. METHODS:One hundred and twenty-six renal transplant patients were recruited. Bl...
journal_title：Acta pharmacologica Sinica
pub_type： 临床试验,杂志文章
doi：10.1038/aps.2012.136
更新日期：2012-12-01 00:00:00
abstract：:Contact inhibition and its disruption of vascular smooth muscle cells (VSMCs) are important cellular events in vascular diseases. But the underlying molecular mechanisms are unclear. In this study we investigated the roles of microRNAs (miRNAs) in the contact inhibition and its disruption of VSMCs and the molecular me...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2018.6
更新日期：2018-05-01 00:00:00
