Skip to main content Accessibility help

Propofol-induced calcium signalling and actin reorganization within breast carcinoma cells

  • V. Garib (a1), K. Lang (a1), B. Niggemann (a1), K. S. Zänker (a1), L. Brandt (a2) and T. Dittmar (a1)...



Background and objective: MDA-MB-468 breast carcinoma cells respond to non-volatile anaesthetics such as propofol with an increased migration. Here we investigated the relationship between GABA-A receptor modulators, the mode of calcium oscillation and actin reorganization with regard to breast carcinoma cell migration. Methods: Expression of the GABA-A receptor was determined by Western blot analysis. Calcium-imaging experiments of individual MDA-MB-468 cells as well as visualization of the F-actin distribution were performed by confocal laser scanning microscopy. Cell migration was investigated in a three-dimensional collagen matrix by time-lapse video microscopy. The GABA agonist propofol was used in a final concentration of 6 μg mL−1. GABA-A receptor antagonist bicuculline (50 μmol) and selective L-type calcium channel blocker verapamil (5 μmol) were used to modulate the propofol effects. Results: A functional GABA-A receptor is expressed by MDA-MB-468 cells. Activation with propofol resulted in sustained increased intracellular calcium concentrations concomitant with actin reorganization and induction of migration in MDA-MB-468 cells. These propofol effects were completely blocked by verapamil. Spontaneous migration of MDA-MB-468 cells (64.4 ± 7.0%) was significantly increased by propofol to 85.0 ± 5.0%. MDA-MB-468 cells co-treated with propofol and verapamil showed a migratory activity of 63.0 ± 2.0% indicating that verapamil blocked the propofol effect. Similar results were achieved with the GABA-A receptor inhibitor bicuculline (control: 56.3 ± 8.5%; propofol: 80.5 ± 7.1%; propofol + bicuculline: 52.5 ± 8.6%). Conclusion: Activation of GABA-A receptor by propofol correlated with an increased migration of MDA-MB-468 breast carcinoma cells, mediated by calcium influx via L-type calcium channels and reorganization of the actin cytoskeleton.


Corresponding author

Correspondence to: Dr Thomas Dittmar, Institute of Immunology, University of Witten/Herdecke, Stockumer Strasse 10, 58448 Witten, Germany. E-mail:; Tel: +49 2302 926 165; Fax: +49 2302 926 158


Hide All


Mikawa K, Akamatsu H, Nishina K et al. Propofol inhibits human neutrophil functions. Anesth Analg 1998; 87: 695700.
Krumholz W, Reussner D, Hempelmann G. The influence of several intravenous anaesthetics on the chemotaxis of human monocytes in vitro. Eur J Anaesthesiol 1999; 16: 547549.
Hunter JD. Effects of anaesthesia on the human immune system. Hosp Med 1999; 60: 658663.
Chen RM, Wu CH, Chang HC et al. Propofol suppresses macrophage functions and modulates mitochondrial membrane potential and cellular adenosine triphosphate synthesis. Anesthesiology 2003; 98: 11781185.
Krumholz W, Abdulle O, Knecht J, Hempelmann G. Effects of i.v. anaesthetic agents on the chemotaxis of eosinophils in vitro. Br J Anaesth 1999; 83: 333335.
Nagata T, Kansha M, Irita K, Takahashi S. Propofol inhibits FMLP-stimulated phosphorylation of p42 mitogen-activated protein kinase and chemotaxis in human neutrophils. Br J Anaesth 2001; 86: 853858.
Beilin B, Shavit Y, Hart J et al. Effects of anesthesia based on large versus small doses of fentanyl on natural killer cell cytotoxicity in the perioperative period. Anesth Analg 1996; 82: 492497.
Hofbauer R, Kaye AD, Kapiotis S, Frass M. The immune system and the effects of non-volatile anesthetics on neutrophil transmigration through endothelial cell monolayers. Curr Pharm Des 1999; 5: 10151027.
Hofbauer R, Frass M, Salfinger H et al. Propofol reduces the migration of human leukocytes through endothelial cell monolayers. Crit Care Med 1999; 27: 18431847.
Galley HF, Dubbels AM, Webster NR. The effect of midazolam and propofol on interleukin-8 from human polymorphonuclear leukocytes. Anesth Analg 1998; 86: 12891293.
Dittmar T, Husemann A, Schewe Y et al. Induction of cancer cell migration by epidermal growth factor is initiated by specific phosphorylation of tyrosine 1248 of c-erbB-2 receptor via EGFR. FASEB J 2002; 16: 18231825.
Szczaurska K, Mazurkiewicz M, Opolski A. The role of GABA-ergic system in carcinogenesis. Postepy Hig Med Dosw 2003; 57: 485500.
Mazurkiewicz M, Opolski A, Wietrzyk J, Radzikowski C, Kleinrok Z. GABA level and GAD activity in human and mouse normal and neoplastic mammary gland. J Exp Clin Cancer Res 1999; 18: 247253.
Opolski A, Mazurkiewicz M, Wietrzyk J, Kleinrok Z, Radzikowski C. The role of GABA-ergic system in human mammary gland pathology and in growth of transplantable murine mammary cancer. J Exp Clin Cancer Res 2000; 19: 383390.
Garib V, Niggemann B, Zanker KS, Brandt L, Kubens BS. Influence of non-volatile anesthetics on the migration behavior of the human breast cancer cell line MDA-MB-468. Acta Anaesthesiol Scand 2002; 46: 836844.
Mammoto T, Mukai M, Mammoto A et al. Intravenous anesthetic, propofol inhibits invasion of cancer cells. Cancer Lett 2002; 184: 165170.
Hales TG, Lambert JJ. The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurones. Br J Pharmacol 1991; 104: 619628.
Krasowski MD, Jenkins A, Flood P et al. General anesthetic potencies of a series of propofol analogs correlate with potency for potentiation of gamma-aminobutyric acid (GABA) current at the GABA(A) receptor but not with lipid solubility. J Pharmacol Exp Ther 2001; 297: 338351.
Katterle Y, Brandt BH, Dowdy SF et al. Antitumour effects of PLC-gamma1-(SH2)(2)-TAT fusion proteins on EGFR/ c-erbB-2-positive breast cancer cells. Br J Cancer 2004; 90: 230235.
Hardwick M, Cavalli LR, Barlow KD, Haddad BR, Papadopoulos V. Peripheral-type benzodiazepine receptor (PBR) gene amplification in MDA-MB-231 aggressive breast cancer cells. Cancer Genet Cytogenet 2002; 139: 4851.
Jiang Y, Harlocker SL, Molesh DA et al. Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarrays. Oncogene 2002; 21: 22702282.
Akinci MK, Schofield PR. Widespread expression of GABA(A) receptor subunits in peripheral tissues. Neurosci Res 1999; 35: 145153..
Kassis J, Moellinger J, Lo H et al. A role for phospholipase C-gamma-mediated signaling in tumor cell invasion. Clin Cancer Res 1999; 5: 22512260.
Oscarsson A, Massoumi R, Sjolander A, Eintrei C. Reorganization of actin in neurons after propofol exposure. Acta Anaesthesiol Scand 2001; 45: 12151220.
Labrakakis C, Patt S, Hartmann J, Kettenmann H. Functional GABA(A) receptors on human glioma cells. Eur J Neurosci 1998; 10: 231238.
Striessnig J, Grabner M, Mitterdorfer J et al. Structural basis of drug binding to L Ca2+ channels. Trends Pharmacol Sci 1998; 19: 108115.
Belouchi NE, Roux E, Savineau JP, Marthan R. Interaction of extracellular albumin and intravenous anaesthetics, etomidate and propofol, on calcium signalling in rat airway smooth muscle cells. Fundam Clin Pharmacol 2000; 14: 395400.
Giannone G, Ronde P, Gaire M, Haiech J, Takeda K. Calcium oscillations trigger focal adhesion disassembly in human U87 astrocytoma cells. J Biol Chem 2002; 277: 26 36426 371.
Lang K, Niggemann B, Zanker KS, Entschladen F. Signal processing in migrating T24 human bladder carcinoma cells: role of the autocrine interleukin-8 loop. Int J Cancer 2002; 99: 673680.


Propofol-induced calcium signalling and actin reorganization within breast carcinoma cells

  • V. Garib (a1), K. Lang (a1), B. Niggemann (a1), K. S. Zänker (a1), L. Brandt (a2) and T. Dittmar (a1)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed