Calycosin induces apoptosis in adenocarcinoma HT29 cells by inducing cytotoxic autophagy mediated by SIRT1/AMPK-induced inhibition of Akt/mTOR.


:Autophagy promotes cell survival or induces apoptosis in cancer cells. While SIRT1 and AMPK induce autophagy in both normal and cancer cells, Akt and mTOR can inhibit it. Calycosin, a methoxyisoflavone, protects against several types of solid tumours including colorectal cancer. However, the mechanisms behind the antitumour effect of Calycosin remain largely unknown. This study investigates if autophagy mediates the anti-tumourigenesis effect afforded by Calycosin and examines if this effect involves activation of SIRT1 and/or AMPK. Human colorectal (HT29) carcinoma cells were cultured under normal conditions with Calycosin (50 μmol/L) in the presence or absence of chloroquine (10 μmol/L), EX-527 (100 nmol/L, SIRT1 inhibitor), or IGF-1 (100 ng/mL, Akt/mTOR activator) for 48 hours. Calycosin inhibited cell growth, proliferation and invasion and increased protein levels of Beclin-1 and LC3II, markers of autophagy. It significantly increased protein levels of cleaved caspase-3, Bax, and SIRT1, and activity of AMPK and reduced those of Bcl-2. These effects were parallel with concomitant reduction in protein levels p-src, integrin-β1 and Cyclin-D1 and activities of Akt and mTOR. Inhibition of autophagy by CQ reversed all these effects except cell invasion. Interestingly, co-incubating the cells with either EX-527 or IGF-1 completely prevented Calycosin-induced autophagy and all other associated effects and increased cell invasion. Also, blockade of SIRT-1 prevented the activation of AMPK, Akt, and mTOR, suggesting it to be an upstream regulator of these markers. In conclusion, Calycosin stimulates CRC cell apoptosis and inhibits their invasion by acting as SIRT1 activator which induces activation of AMPK-induced inhibition of Akt/mTOR axis.


El-Kott AF,Al-Kahtani MA,Shati AA




Has Abstract


2019-10-01 00:00:00












  • Excess weight in children and adolescents is associated with altered subendocardial blood supply among girls but not boys.

    abstract::Subendocardial viability ratio (SEVR) is a reliable index of myocardial supply-workload balance. This study sought to investigate whether overweight/obese children and adolescents have altered SEVR and to identify which are the associated factors. This cross-sectional study involved 789 individuals. Central haemodynam...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 信件


    authors: Zaniqueli D,Alvim RO,Baldo MP,Luiz SG,Cunha RS,Mill JG

    更新日期:2018-05-01 00:00:00

  • Absence of detectable regression of human hypertensive left ventricular hypertrophy following drug treatment for 1 year.

    abstract::1. The present study was designed to compare and contrast the effects of 1 year's treatment with angiotensin-converting enzyme inhibition (captopril 25-100 mg daily) and beta-blockade (atenolol 50-100 mg daily) on hypertensive cardiac structure and function as well as the other established cardiovascular risk factors ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Laufer E,Reid C,Qi XL,Jennings GL

    更新日期:1998-03-01 00:00:00

  • Relationship between serum osteocalcin and glycaemic variability in Type 2 diabetes.

    abstract::1. Recent reports have described the role of osteocalcin in glucose metabolism and glycaemic variability has been proven to be associated with an increased risk of diabetes complications. However, the relationship between osteocalcin and glycaemic variability remains unclear. The aim of the present study was to examin...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 临床试验,杂志文章


    authors: Bao YQ,Zhou M,Zhou J,Lu W,Gao YC,Pan XP,Tang JL,Lu HJ,Jia WP

    更新日期:2011-01-01 00:00:00

  • Effect of Anoectochilus formosanus on fibrosis and regeneration of the liver in rats.

    abstract::1. The present study examined the effects of an aqueous extract of Anoectochilus formosanus (AFE) on both hepatic fibrosis and regeneration in rats. 2. Fibrosis was induced by intraperitoneal injection of dimethylnitrosamine (DMN) for 3 consecutive days per week for 4 weeks. 3. In DMN-treated rats, liver cirrhosis-ass...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Shih CC,Wu YW,Hsieh CC,Lin WC

    更新日期:2004-09-01 00:00:00

  • Defective intracellular Ca2+ homeostasis contributes to myocyte dysfunction during ventricular remodelling induced by chronic volume overload in rats.

    abstract::1. Previous studies have demonstrated progressive ventricular hypertrophy, dilatation and contractile depression in response to chronic volume overload. Whether this decompensation was related to intrinsic myocyte dysfunction was not clear. The present study evaluated ventricular myocyte function at critical times dur...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Ding YF,Brower GL,Zhong Q,Murray D,Holland M,Janicki JS,Zhong J

    更新日期:2008-07-01 00:00:00

  • Afferent control of vasopressin and renin release during haemorrhage in normal and autonomically blocked rabbits.

    abstract::1. The role of the arterial and cardiac baroreceptors on the arginine vasopressin (AVP) and plasma renin activity (PRA) responses to haemorrhage was studied in conscious rabbits. They were bled at a rate of approximately 3% of their blood volume (BV)/min, both when the autonomic nervous system (ANS) was intact and dur...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Courneya CA,Korner PI,Oliver JR,Woods RL

    更新日期:1992-11-01 00:00:00

  • High-salt diet and responses of the pressurized mesenteric artery of the dog to noradrenaline and acetylcholine.

    abstract::A high-salt diet in rats has been shown to result in enhanced vasoconstrictor and/or reduced vasodilator responses of isolated arteries to agonists. The present experiments were designed to investigate the effects of dietary salt on the responses of the pressurized mesenteric resistance artery of the dog to constricto...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Sofola O,Knill A,Myers D,Hainsworth R,Drinkhill M

    更新日期:2004-10-01 00:00:00

  • Activation of cardiac M3 muscarinic acetylcholine receptors has cardioprotective effects against ischaemia-induced arrhythmias.

    abstract::Increasing evidence indicates the important roles of M(3) muscarinic acetylcholine receptors (M(3) mAChR) in the regulation and maintenance of cardiac function and heart disease. In the present study, we investigated whether the M(3) mAChR mediates the cardioprotection against ischaemia-induced arrhythmias and the ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Wang S,Han HM,Jiang YN,Wang C,Song HX,Pan ZY,Fan K,Du J,Fan YH,Du ZM,Liu Y

    更新日期:2012-04-01 00:00:00

  • Effects of dopamine and nitric oxide on arterial pressure and renal function in volume expansion.

    abstract::1. The aim of the present study was to investigate the role of dopamine (DA) in the hypotensive and renal effects of L-arginine during extracellular fluid volume expansion (10% bodyweight). 2. Animals were randomized to non-expanded and expanded groups. Both groups received different treatments: L-arginine (250 mg/kg,...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Costa Mde L,Loria A,Marchetti M,Balaszczuk AM,Arranz CT

    更新日期:2002-09-01 00:00:00

  • Noradrenergic reinnervation of the rat vas deferens after vasovasostomy following vasectomy.

    abstract::1. Anastomosis (vasovasostomy) of epididymal and prostatic halves of vasa deferentia was carried out in rats in which unilateral or bilateral medial transection (vasectomy) had been performed 4 weeks previously. 2. Noradrenaline levels in epididymal halves of vasa deferentia, 8 weeks after anastomosis with prostatic h...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: DeGaris RM,Pennefather JN

    更新日期:1987-05-01 00:00:00

  • Protective effects of L-carnitine on myoglobinuric acute renal failure in rats.

    abstract::1. Muscle injury (rhabdomyolysis) is one of the causes of acute renal failure (ARF). Iron, free radicals and nitric oxide (NO) play a critical role in the pathogenesis of glycerol-induced myoglobinuric ARF. L-Carnitine is an anti-oxidant and prevents the accumulation of end-products of lipid peroxidation. Therefore, t...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Aydogdu N,Atmaca G,Yalcin O,Taskiran R,Tastekin E,Kaymak K

    更新日期:2006-01-01 00:00:00

  • Differential efficacy of perindopril and enalapril in experimental diabetic nephropathy.

    abstract::1. Treatment with angiotensin converting enzyme (ACE) inhibitors ameliorates human and experimental diabetic nephropathy, possibly as a result of changes in angiotensin II (AngII) and/or bradykinin concentrations. However, ACE is an indiscriminate enzyme, which hydrolyses numerous vasoactive peptides at two catalytic ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Duggan KA,Hodge G,Makarious MM,Charlesworth JA

    更新日期:1996-06-01 00:00:00

  • Effects of amiodarone and L8040, novel antianginal and antiarrhythmic drugs, on cardiac and coronary haemodynamics and on cardiac intracellular potentials.

    abstract::1. The effects on the coronary and systemic haemodynamics of intravenous and intracoronary injections of two benzfuran derivatives, amiodarone and its brominated analogue (L8040), were studied in open-chest anaesthetized dogs. The effects of L8040 on cardiac intracellular potentials after 6 weeks of 20 mg/kg intraperi...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Singh BN,Jewitt DE,Downey JM,Kirk ES,Sonnenblick EH

    更新日期:1976-09-01 00:00:00

  • Mineralocorticoids are not involved in the antihypertensive effect of neonatal thymectomy in the genetically hypertensive LH rat.

    abstract::1. In order to determine whether the antihypertensive effect of neonatal thymectomy in genetically hypertensive rats could be mediated through altered adrenal function, systolic blood pressure (SBP) and urinary excretion of deoxycorticosterone (DOC), corticosterone (B) and aldosterone were measured in thymectomized hy...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Bataillard A,Gomez-Sanchez CE,Vincent M,Touraine JL,Sassard J

    更新日期:1988-11-01 00:00:00

  • Cardiac effects of salbutamol-induced hypokalaemia in the conscious dog.

    abstract::1. Infusion of salbutamol (3.0 microgram/min after a bolus injection of 100 microgram) produced hypokalaemia in conscious dogs. 2. Measurement of arterial and coronary sinus potassium differences revealed no significant potassium loss from the heart with established hypokalaemia. 3. Shortly after the initial salbutamo...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Wahlqvist ML,Shanahan EA,Dennis PM,Pullan PT,Wilmshurst EG

    更新日期:1978-11-01 00:00:00

  • Stimulation of phosphatidylinositol turnover in adult rat left atria does not involve release of inositol(1,4,5)trisphosphate.

    abstract::1. The turnover rate of inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) in noradrenaline-stimulated adult rat left atria was calculated from changes in specific activity and was found to equal 110 ct/min per mg tissue. In contrast, the isomers of inositol mono- and bisphosphates accumulated at a rate of 508 ct/min per mg....

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Anderson KE,Myers D,Woodcock EA

    更新日期:1993-05-01 00:00:00

  • Chronic consumption of a high-fat diet rich in corn oil activates intrinsic cell death pathway and induces several ultrastructural changes in the atria of healthy and type 1 diabetic rat.

    abstract::This study investigates the effect of chronic consumption of a high-fat diet rich in corn oil (CO-HFD) on atrial cells ultrastructure, antioxidant levels and markers of intrinsic cell death of both control and type 1 diabetes mellitus (T1DM)-induced rats. Adult male rats (10 rats/group) were divided into four groups: ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Eid RA,Eleawa SM,Alkhateeb MA,Aldera H,Zaki MSA,Al-Shraim M,Saeed MA,El-Kott AF,Alaa Eldeen M,Alassiri M,Alshehri MM,Salem Al-Shudiefat AA,Khalil MA

    更新日期:2019-12-01 00:00:00

  • Species differences in binding of submandibular nuclear proteins to renin promoter DNA.

    abstract::1. Renin is highly expressed in submandibular gland (SMG) of mouse, which has two genes, Ren-1d and Ren-2d, but not at all in rat SMG. Differences in nuclear protein binding to renin promoter DNA were, therefore, explored. 2. Rat -169 to +23 renin DNA formed complexes with both mouse and rat extract, whereas a corresp...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Loudon JA,Fukamizu A,Murakami K,Morris BJ

    更新日期:1993-05-01 00:00:00

  • Postnatal outcomes in term and preterm lambs following fetal growth restriction.

    abstract::1. Epidemiological evidence indicates that low birthweight increases the risk of a number of adult-onset diseases. It is now apparent that many babies with a low birthweight may have been subjected to a combination of reduced growth rates in utero as well as preterm birth. However, the long-term effects of preterm bir...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Cock ML,Camm EJ,Louey S,Joyce BJ,Harding R

    更新日期:2001-11-01 00:00:00

  • Investigation of class I anti-arrhythmic drug actions on guinea-pig cardiac mitochondrial lactate dehydrogenase activity.

    abstract::1. The effects of the Class I anti-arrhythmic drugs quinidine, procainamide, lidocaine, phenytoin and tocainide on mitochondrial lactate dehydrogenase activity were compared in guinea-pig heart preparations. 2. All the tested drugs inhibited the enzyme activity in a concentration-dependent fashion, exhibiting varying ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Dzimiri N,Almotrefi AA

    更新日期:1993-04-01 00:00:00

  • Effects of rilmenidine on proximal tubular fluid absorption in rats.

    abstract::The antihypertensive agent rilmenidine has threefold higher affinity for I(1) imidazoline receptors compared with alpha(2)-adrenoceptors and acts on the central nervous system by reducing sympathetic activity and in the kidney by inhibiting Na(+)/H(+) exchange activity. In the present study, we examined: (i) the effec...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Jovanovska V,Eitle E,Harris PJ

    更新日期:2004-05-01 00:00:00

  • Effects of 17 beta-oestradiol on vascular responses in the in situ blood-perfused mesentery of Wistar-Kyoto rats.

    abstract::1. To determine whether endogenous oestrogen plays a role in pregnancy induced decreased vascular reactivity we have examined the effects of 17 beta-oestradiol on vasoconstrictor responses to various stimuli using an in situ blood-perfused mesenteric vascular preparation in Wistar-Kyoto (WKY) rats. 2. Daily administra...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Chu ZM,Beilin LJ

    更新日期:1997-06-01 00:00:00

  • Influence of variation in dietary sodium intake on biochemical indices of sympathetic activity in normal man.

    abstract::The effects of variation in dietary sodium intake on biochemical indices of sympathetic activity were investigated in normal subjects. Sodium restriction for 7 days (mean urinary sodium excretion 21 mmol/day, s.e.m. = 4) increased supine plasma noradrenaline concentration significantly (1.78 nmol/l, s.e.m. = 0.23) com...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Watson RD,Esler MD,Leonard P,Korner PI

    更新日期:1984-03-01 00:00:00

  • Brain and retinal microglia in health and disease: an unrecognized target of the renin-angiotensin system.

    abstract::Microglia are the resident immune cells within the brain and retina, commonly known as the macrophages of the central nervous system (CNS). Microglia survey the surrounding milieu to eliminate invading microbes, clear cellular debris and enforce programmed cell death by removing apoptotic cells. Complementary to their...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审


    authors: McCarthy CA,Widdop RE,Deliyanti D,Wilkinson-Berka JL

    更新日期:2013-08-01 00:00:00

  • The intrauterine renin-angiotensin system: Sex-specific effects on the prevalence of spontaneous preterm birth.

    abstract::Preterm birth (PTB) is the single largest cause of death in infants and young children. The rate of PTB is significantly higher in male infants, particularly those that are born very preterm. Here we present evidence to suggest that the decidual renin-angiotensin system may play a role in inhibiting inflammation and m...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审


    authors: Pringle KG,Zakar T,Lumbers ER

    更新日期:2017-05-01 00:00:00

  • Recent developments concerning diet and hypertension.

    abstract::1. Recent data from randomized controlled dietary trials have shown blood pressure-lowering effects of foodstuffs and dietary patterns to be of practical importance for both individual and population blood pressure control. 2. The salient studies include Dietary Approaches to Stop Hypertension (DASH) trials, on comple...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Beilin LJ,Burke V,Puddey IB,Mori TA,Hodgson JM

    更新日期:2001-12-01 00:00:00

  • Characterisation of a rat model of mechanical low back pain at an advanced stage using immunohistochemical methods.

    abstract::Chronic low back pain (LBP) has high prevalence in the adult population which is associated with enormous disability. Hence, our aim was to further characterise our LBP rat model by using immunohistological and immunohistochemical methods at an advanced stage (day 49) of the model. Male Sprague-Dawley rats were anaest...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Park TSW,Khan N,Kuo A,Nicholson JR,Corradini L,Smith MT

    更新日期:2020-09-05 00:00:00

  • Ageing and blood pressure regulation: dose-response relationships for angiotensin, blood pressure, atrial natriuretic peptide and aldosterone in normal subjects of varying ages.

    abstract::1. Infusion of increasing doses of angiotensin II (AII) in normal subjects sequentially increased blood pressure, aldosterone and atrial natriuretic peptide (ANP) levels. 2. The slope of ANP response to AII was positively correlated with basal ANP and with the slope of blood pressure response to AII (pressor slope) bu...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Finn WL,Tunny TJ,Klemm SA,Ryan SJ,Gordon RD

    更新日期:1993-05-01 00:00:00

  • Effects of econazole on Ca2+ levels in and the growth of human prostate cancer PC3 cells.

    abstract::1. Econazole is used clinically as an antifungal drug with many different in vitro effects. However, the effects of econazole on prostate cancer cells are unknown. The effects of econazole on intracellular Ca2+ concentrations ([Ca2+]i) in and the proliferation of human PC3 prostate cancer cells was explored in the pre...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Huang JK,Liu CS,Chou CT,Liu SI,Hsu SS,Chang HT,Hsieh CH,Chang CH,Chen WC,Jan CR

    更新日期:2005-09-01 00:00:00

  • Resistance of sympathetic cardiac nerve function in the pithed rat to prejunctional effects of angiotensin II.

    abstract::1. The spinal sympathetic outflow (C7-T2) of pithed male Wistar rats was electrically stimulated (30-50 V, 0.5 ms, 0.1-1.0 Hz) and heart rate and arterial blood pressure were recorded. D-Tubocurarine (1 mg/kg) and atropine (1 mg/kg) were administered intravenously (i.v.) to reduce voluntary and parasympathetic nerve a...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Rechtman MP,King RG,Boura AL

    更新日期:1988-12-01 00:00:00