Mitochondrial targeting drug lonidamine triggered apoptosis in doxorubicin-resistant HepG2 cells.

Abstract:

:Mitochondria play a crucial role in the induction and execution of apoptosis. Accordingly, recent suggestions have been made to use agents that directly act on mitochondria to trigger apoptosis so that drug-sensitive and-resistant tumour cells can be eliminated. To test this hypothesis, human hepatocarcinoma HepG2 and its derivative R-HepG2 with doxorubicin (Dox) resistance as a result of expression of P-glycoprotein were used to investigate the effect of lonidamine (LND), a new mitochondrial targeting drug, on the induction of apoptosis. Results from our study indicate that R-HepG2 cells were more sensitive to LND than parental cells in terms of cytotoxicity determined by alamar blue assay. Cell death induced by LND was associated with the hallmarks of apoptosis such as mitochondrial membrane depolarization, release of cytochrome c, phosphatidyl-serine externalization and DNA fragmentation. Moreover, combined treatment of cells with Dox and LND elicited more cell death. Taken together, our results suggest a potential use of LND as an anti-cancer drug to bypass drug resistance and to trigger tumour destruction through apoptosis in HepG2 and R-HepG2 cells.

journal_name

Life Sci

journal_title

Life sciences

authors

Li YC,Fung KP,Kwok TT,Lee CY,Suen YK,Kong SK

doi

10.1016/s0024-3205(02)02103-3

subject

Has Abstract

pub_date

2002-10-25 00:00:00

pages

2729-40

issue

23

eissn

0024-3205

issn

1879-0631

pii

S0024320502021033

journal_volume

71

pub_type

杂志文章
  • Transport and toxic mechanism for aluminum citrate in human neuroblastoma SH-SY5Y cells.

    abstract::Aluminum (Al) is thought to be a risk factor for neurodegenerative disorders, but the molecular mechanism has been not clarified yet. In this study, we examined how a transport system handled transport of Al citrate, the major Al species in brain, and effect of Al citrate treatment on expression of the transporter and...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2005.12.048

    authors: Nagasawa K,Akagi J,Koma M,Kakuda T,Nagai K,Shimohama S,Fujimoto S

    更新日期:2006-05-30 00:00:00

  • Therapeutic potential of CNS-active M2 antagonists: novel structures and pharmacology.

    abstract::Clinical trials with muscarinic agonists or acetylcholine esterase inhibitors for the treatment of Alzheimer's dementia have shown disappointing or equivocal results. An alternative treatment of this disease is the development of drugs which enhance the release of acetylcholine. It is believed, that of the five muscar...

    journal_title:Life sciences

    pub_type: 杂志文章,评审

    doi:10.1016/0024-3205(93)90307-o

    authors: Doods HN,Quirion R,Mihm G,Engel W,Rudolf K,Entzeroth M,Schiavi GB,Ladinsky H,Bechtel WD,Ensinger HA

    更新日期:1993-01-01 00:00:00

  • Molluscicidal and piscicidal activities of Venezuelan Chrysobalanaceae plants.

    abstract::Extracts of increasing polarity of 6 Venezuelan plants belonging to the Chrysobalanaceae family were tested for possible letal toxicity against Biomphalaria glabrata Say, a snail intermediate hosts of Schistosoma mansoni Sambon. The piscicidal toxicity of the active extracts was also evaluated with the aim of findings...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(99)00600-1

    authors: Bilia AR,Braca A,Mendez J,Morelli I

    更新日期:2000-01-01 00:00:00

  • Endogenous opioids, circadian rhythms, nutrient deprivation, eating and drinking.

    abstract::Immunoreactive (ir) beta-endorphin (b-END) and dynorphin (DYN) in rat brain and pituitary were measured after food and water deprivation and from brains taken during either day or night. In other rats, eating and drinking were measured following lesions in the arcuate n. Ir-DYN levels are higher in hypothalamus and lo...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(82)90221-1

    authors: Reid LD,Konecka AM,Przewłocki R,Millan MH,Millan MJ,Herz A

    更新日期:1982-10-18 00:00:00

  • The stimulatory and inhibitory effects of quinpirole hydrochloride, D2-dopamine receptor agonist, on secretion of prolactin as assessed by the reverse hemolytic plaque assay.

    abstract::Recent findings indicate that low concentrations of dopamine (DA) stimulate the secretion of prolactin (PRL) in vitro. In this study, we found that low concentrations of the highly-specific DA D2 receptor agonist, quinpirole hydrochloride (LY) stimulate PRL secretion in female rats, assessed by reverse hemolytic plaqu...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(93)90749-s

    authors: Niimi M,Takahara J,Sato M,Murao K,Kawanishi K

    更新日期:1993-01-01 00:00:00

  • Relationship between noradrenaline release in the locus coeruleus and antiallodynic efficacy of analgesics in rats with painful diabetic neuropathy.

    abstract:AIMS:In animal models of neuropathic pain, the noradrenergic descending pain inhibitory pathways from the locus coeruleus (LC) may be suppressed. However, no study has investigated the correlation between noradrenaline (NA) release in the LC and efficacy of analgesics in rats with painful diabetic neuropathy. Using mic...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2013.04.015

    authors: Suehiro K,Funao T,Fujimoto Y,Yamada T,Mori T,Nishikawa K

    更新日期:2013-06-21 00:00:00

  • Evidence that diclofenac and celecoxib are thyroid hormone receptor beta antagonists.

    abstract:UNLABELLED:Long term use of NSAIDs is linked to side effects such as gastric bleeding and myocardial infarction. AIMS:Use of in silico methods and pharmacology to investigate the potential for NSAIDs diclofenac, celecoxib and naproxen to bind to nuclear receptors. MATERIALS AND METHODS:In silico screening predicted t...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2016.01.013

    authors: Zloh M,Perez-Diaz N,Tang L,Patel P,Mackenzie LS

    更新日期:2016-02-01 00:00:00

  • Prenatal exposure to low levels of carbon monoxide alters sciatic nerve myelination in rat offspring.

    abstract::Prenatal exposure to low concentrations of carbon monoxide (CO, 75 and 150 ppm from day 0 to day 20 of gestation), resulting in maternal blood HbCO concentrations equivalent to those maintained by human cigarette smokers, leads to subtle myelin alterations in the sciatic nerve of male rat offspring. The rapid growth s...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(00)00761-x

    authors: Carratù MR,Cagiano R,Desantis S,Labate M,Tattoli M,Trabace L,Cuomo V

    更新日期:2000-08-25 00:00:00

  • Tributyltin inhibits osteoblastic activity and disrupts calcium metabolism through an increase in plasma calcium and calcitonin levels in teleosts.

    abstract::To examine the direct effects of tributyltin acetate (TBTA) on osteoclasts and osteoblasts, teleost scale, which has both osteoclasts and osteoblasts and is similar to mammalian membrane bone, was used in the present study. The activities of tartrate-resistant acid phosphatase and alkaline-phosphatase, as respective i...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2005.10.004

    authors: Suzuki N,Tabata MJ,Kambegawa A,Srivastav AK,Shimada A,Takeda H,Kobayashi M,Wada S,Katsumata T,Hattori A

    更新日期:2006-04-18 00:00:00

  • Actinomycin D inhibition of monoclonal antibody binding to nucleolar phosphoprotein 37/5.2 (B23).

    abstract::Actinomycin D was found to block binding of a monoclonal antibody to nucleolar phosphoprotein 37/5.2 (B23) when incubated either simultaneously with or prior to addition of the antibody. Daunorubicin had no significant blocking activity of this antigen-antibody reaction. In comparative studies with a monoclonal antibo...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(84)90275-3

    authors: Busch RK,Chan PK,Busch H

    更新日期:1984-10-22 00:00:00

  • Lamotrigine, a mood stabilizer, may have beneficial effects on memory acquisition and retrieval in mice.

    abstract:AIMS:The aim of this study was to investigate the effects of a mood stabilizer lamotrigine (LMG) on learning and memory processes using Morris water maze (MWM), modified elevated plus maze (mEPM) and passive avoidance (PA) tests. MAIN METHODS:Balb-c mice were used. LMG were injected (20; 40mg/kg, intraperitoneal, i.p....

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2012.09.020

    authors: Celikyurt IK,Ulak G,Mutlu O,Akar FY,Erden F,Komsuoglu SS

    更新日期:2012-12-17 00:00:00

  • Oral magnesium administration prevents vascular complications in STZ-diabetic rats.

    abstract::Vascular disease is one of the complicating features of diabetes mellitus. Magnesium deficiency has recently been proposed as a novel factor implicated in the pathogenesis of diabetes complications. Several studies have indicated that hypertension in diabetic patients is an independent altered reaction of blood vessel...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2004.07.027

    authors: Soltani N,Keshavarz M,Sohanaki H,Dehpour AR,Zahedi Asl S

    更新日期:2005-02-11 00:00:00

  • Up-regulation of cyclinD1 and Bcl2A1 by insulin is involved in osteoclast proliferation.

    abstract:AIMS:Insulin receptor signaling in osteoblasts has been well established, but the effects of insulin on osteoclast proliferation are poorly explored. The objective of this study was to investigate the roles and the mechanisms of insulin on osteoclast proliferation. MAIN METHODS:After insulin treatment to primary osteo...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2014.07.006

    authors: Lee JY,Lee NK

    更新日期:2014-10-02 00:00:00

  • Differential sensitivity to cocaine in spontaneously hypertensive and Wistar-Kyoto rats.

    abstract::Physiological, pharmacological and toxicological responses to two regimens of cocaine administration were compared between spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. An initial experiment examined renal excretory and hemodynamic function in response to an acute volume load in anesthetized SHR and WK...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(89)90254-3

    authors: Ishizuka Y,Rockhold RW,Kirchner K,Hoskins B,Ho IK

    更新日期:1989-01-01 00:00:00

  • Evidence for a mitochondrial lesion in cystic fibrosis.

    abstract::Cystic fibrosis (CF) remains a major problem in human genetics and cell pathophysiology. It is a single gene trait caused by a mutation on the long arm of chromosome 7. Among its expressions are abnormal regulation of chloride channels and/or microobstructions in exocrine tissues. Here, evidence is presented that mito...

    journal_title:Life sciences

    pub_type: 杂志文章,评审

    doi:10.1016/0024-3205(89)90389-5

    authors: Shapiro BL

    更新日期:1989-01-01 00:00:00

  • Effect of estradiol and relaxin on collagen and non-collagen protein synthesis by mammary fibroblasts.

    abstract::In order to determine the effect of relaxin and estradiol on collagen and noncollagen synthesis by mammary gland fibroblasts, fibroblasts isolated from guinea pig mammary glands were grown on plastic or Cytodex-3 collagen coated microcarriers. On plastic, estradiol (600 pg/ml) increased the incorporation of tritiated ...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(84)90460-0

    authors: Sheffield LG,Anderson RR

    更新日期:1984-11-26 00:00:00

  • Central nervous system lipid alterations in rats with experimental allergic encephalomyelitis and its suppression by immunosuppressive drugs.

    abstract::Rats with experimental allergic encephalomyelitis (EAE) induced with myelin or spinal cord show decreases in the content of sulphatides and cerebrosides and increases in the level of esterified cholesterol in the CNS. In this work it is shown that brain sulphatide changes can be obtained by injection of mixtures conta...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(82)90600-2

    authors: Roth GA,Monferran CG,Maggio B,Cumar FA

    更新日期:1982-03-08 00:00:00

  • Oral contraceptive use and increased plasma concentration of C-reactive protein.

    abstract::We examined, in young adult women, the association between current low dose oral contraceptive (OC) use and plasma levels of C-reactive protein (CRP), an acute phase reactant predictive of cardiovascular disease risk. We conducted a cross-sectional analysis of 30 healthy, non-smoking, non-obese women (18 OC users and ...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(03)00425-9

    authors: Dreon DM,Slavin JL,Phinney SD

    更新日期:2003-07-25 00:00:00

  • cDNA microarray analysis of the differentially expressed genes involved in murine pre-osteoclast RAW264.7 cells proliferation stimulated by dexamethasone.

    abstract::Glucocorticoids (GCs) are hormones with anti-inflammatory and immuno-suppressive effects. The use of hormonal medicine like GCs may cause systemic adverse effects. In the present study, the cellular response of murine pre-osteoclast cell line RAW264.7 to dexamethasone (DEX) was investigated and the result demonstrated...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2007.10.012

    authors: Zhang Q,Fong CC,Zhang Y,Tzang CH,Fong WF,Yang M

    更新日期:2008-01-16 00:00:00

  • Kappa opiate agonist RU 51599 inhibits vasopressin gene expression and osmotically-induced vasopressin secretion in vitro.

    abstract::Kappa (kappa) opioid agonists induce a water diuresis and inhibit vasopressin (AVP) secretion. Hypothalamic and neurohypophysial sites have both been implicated in the response. The present study was designed to ascertain if kappa-agonist inhibition of osmotically-stimulated AVP secretion is associated with parallel c...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(97)00931-4

    authors: Rossi NF,Kim JK,Summers SN,Schrier RW

    更新日期:1997-01-01 00:00:00

  • Studies on alpha 2-adrenergic modulation of hypothalamic somatostatin secretion in rats.

    abstract::This study was undertaken to investigate whether or not alpha 2-adrenergic pathways would negatively modulate the hypothalamic somatostatin release in rats. To induce pharmacological changes in SS release, three groups of male Sprague-Dawley rats (n = 30/group) were separately anesthetized by ip administration of uret...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(93)90277-a

    authors: Lima L,Arce V,Tresguerres JA,Devesa J

    更新日期:1993-01-01 00:00:00

  • Norepinephrine release during vasoconstriction induced by cross-linked hemoglobin.

    abstract::The pressor effect of hemoglobin-based blood substitutes is due partly to their capacity to scavenge nitric oxide (NO), a potent vasodilator. NO also appears to modulate the release of norepinephrine (NE) from sympathetic nerve endings in some blood vessels. Thus studies were designed to determine if contraction occur...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(96)00269-x

    authors: Hunter LW,Tyce GM,Rorie DK

    更新日期:1996-01-01 00:00:00

  • Evidence from binding studies for beta 1-adrenoceptors associated with glomeruli isolated from rat kidney.

    abstract::The beta adrenoceptor antagonist radioligand [3H] dihydroalprenolol (DHA) has been used to characterise beta adrenoceptors in membranes prepared from rat renal glomeruli. Association of the ligand was rapid and had reached equilibrium within 10 mins at 37 degrees C. Dissociation occurred in two distinct phases, a rapi...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(83)90715-4

    authors: McPherson GA,Summers RJ

    更新日期:1983-07-04 00:00:00

  • Delay of puberty and impairment of growth in female rats given a non competitive antagonist of NMDA receptors.

    abstract::Reportedly, excitatory amino acids are involved in the control of gonadotropin secretion of rats and non-human primates. The aim of this study was to investigate the effect of chronic blockade of NMDA (N-methyl-D-aspartic acid) receptors by the non competitive receptor antagonist MK-801 on gonadotropin secretion and t...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(90)90218-g

    authors: Veneroni O,Cocilovo L,Müller EE,Cocchi D

    更新日期:1990-01-01 00:00:00

  • Endothelium inhibits the palytoxin-induced depolarization and Ca2+ mobilization in porcine coronary artery through endothelium-derived hyperpolarizing factor and nitric oxide released by palytoxin.

    abstract::Palytoxin induced increases in cytosolic Ca2+ and tension, which were dependent on external Ca2+, and depolarized the membrane in endothelium-denuded porcine coronary arteries. When the endothelium was present, however, these effects were greatly inhibited, suggesting that some factors from endothelium inhibited the p...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(96)00682-0

    authors: Ishii K,Ito KM,Ikeda M,Uemura D,Ito K

    更新日期:1997-01-01 00:00:00

  • PK 11195, an antagonist of peripheral type benzodiazepine receptors, modulates Bay K8644 sensitive but not beta- or H2-receptor sensitive voltage operated calcium channels in the guinea pig heart.

    abstract::In a partially depolarized guinea pig papillary muscle preparation, BAY K8644 stimulated voltage-operated calcium channels, promoting slow action potentials; this effect was dose-dependent over a concentration range of 3 X 10(-7) M to 3 X 10(-6) M. Isoproterenol and histamine also induced slow action potentials by sti...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(86)90651-x

    authors: Mestre M,Carriot T,Néliat G,Uzan A,Renault C,Dubroeucq MC,Guérémy C,Doble A,Le Fur G

    更新日期:1986-07-28 00:00:00

  • Specific ganglioside binding to receptor sites on T lymphocytes that couple to ganglioside-induced decrease of CD4 expression.

    abstract::The binding of different gangliosides to rat T-helper lymphocytes was characterized under conditions that decrease CD4 expression on different mammalian T-helper lymphocytes. Saturation binding by monosialylated [3H]-GM1 to rat T-lymphocytes was time- and temperature-dependent, had a dissociation constant (KD) of 2.2 ...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(89)90123-9

    authors: Morrison WJ,Offner H,Vandenbark AA

    更新日期:1989-01-01 00:00:00

  • A spinal site mediates opiate analgesia in frogs.

    abstract::The application of acetic acid to the hind leg of a frog will induce a spinally mediated wiping reflex only if the acetic acid concentration is above a certain threshold. By using this reflex as the basis of a test for nociception, we show that morphine sulfate is a potent analgesic in the frog when injected into the ...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(83)90333-8

    authors: Stevens CW,Pezalla PD

    更新日期:1983-11-21 00:00:00

  • Mitochondrial ultrastructure and density in a primate model of persistent tardive dyskinesia.

    abstract::The use of neuroleptic drugs to treat schizophrenia is almost invariably associated with extrapyramidal movement disorders. One of these disorders, tardive dyskinesia (TD), can persist long after neuroleptic withdrawal suggesting that permanent neurological damage is produced. However, there appears to be no convincin...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(00)00442-2

    authors: Eyles DW,Pond SM,Van der Schyf CJ,Halliday GM

    更新日期:2000-02-25 00:00:00

  • Chinese medicinal herbs Muh-Shiang Bin-Lang-Wan increases the motility of sphincter of Oddi in anesthetized rabbits through activation of M1 muscarinic receptors.

    abstract::The sphincter of Oddi (SO) plays an important role in regulating the bile flow into the duodenum. This study was designed to investigate the effect of Chinese Medicinal Herbs Muh-Shiang-Bin-Lang-Wan (MSBLW) and their mechanism of action on regulating the motility of SO in rabbits. The activity of SO in anesthetized ra...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2003.09.032

    authors: Kuo YI,Chiu JH,Lin JG,Hsieh CL,Wu CW

    更新日期:2003-12-12 00:00:00