Sanguinarine overcomes P-glycoprotein-mediated multidrug-resistance via induction of apoptosis and oncosis in CEM-VLB 1000 cells

Priya Weerasinghe, Sarathi Hallock, Shou-Ching Tang, Benjamin Trump, Andrejs Liepins

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Permeability-glycoprotein (Pgp) positive cells are known to be encoded by the multidrug-resistance gene (MDR1), and characterized by a reduced ability to accumulate drugs. The vinblastin-resistant, Pgp positive CEM-VLB 1000 and its wild type (Pgp-negative and vinblastin-sensitive) counterpart CEM-T4 human leukemia cells, when treated with the alkaloid sanguinarine, were both found to undergo apoptosis at concentrations of 1.5 μg/ml and oncosis/blister cell death (BCD) at concentrations of 12.5 μg/ml. The aim of this study was to assess the ability of sanguinarine to overcome Pgp-mediated multidrug-resistance (MDR), and also to characterize the cell death processes of apoptosis and oncosis (or bimodal cell death) induced by sanguinarine in MDR cells. The cell death processes of apoptosis and oncosis in CEM-VLB 1000 and CEM-T4 cell lines were found to be qualitatively similar when assessed by light microscopy, terminal deoxynucleotidyl transferase (TdT) end-labeling, annexin-V-binding, trypan blue exclusion and western blot analysis. Western blotting revealed an increase in the Bax/Bcl-2 ratio and activation of caspase-3 in apoptosis but not oncosis in both cell lines. The Pgp-positive CEM-VLB 1000 cells and their wild type CEM-T4 cells were both equally sensitive to sanguinarine. Thus, sanguinarine may overcome the phenomenon of Pgp-mediated MDR by inducing apoptosis through increasing the Bax/Bcl-2 ratio and activating caspase-3, and oncosis, which involved neither.

Original languageEnglish (US)
Pages (from-to)21-30
Number of pages10
JournalExperimental and Toxicologic Pathology
Volume58
Issue number1
DOIs
StatePublished - Aug 15 2006

Fingerprint

Multiple Drug Resistance
P-Glycoprotein
Permeability
Glycoproteins
Cell death
Apoptosis
Cell Death
CD4-Positive T-Lymphocytes
Cells
Caspase 3
Western Blotting
MDR Genes
Cell Line
Trypan Blue
DNA Nucleotidylexotransferase
Annexin A5
Blister
Alkaloids
Labeling
Optical microscopy

Keywords

  • Anticancer-agent
  • Apoptosis
  • Bimodal cell death
  • Lymphoma
  • Multidrug-resistance
  • Necrosis
  • Oncosis
  • P-glycoprotein
  • Sanguinarine

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Cell Biology

Cite this

Sanguinarine overcomes P-glycoprotein-mediated multidrug-resistance via induction of apoptosis and oncosis in CEM-VLB 1000 cells. / Weerasinghe, Priya; Hallock, Sarathi; Tang, Shou-Ching; Trump, Benjamin; Liepins, Andrejs.

In: Experimental and Toxicologic Pathology, Vol. 58, No. 1, 15.08.2006, p. 21-30.

Research output: Contribution to journalArticle

Weerasinghe, Priya ; Hallock, Sarathi ; Tang, Shou-Ching ; Trump, Benjamin ; Liepins, Andrejs. / Sanguinarine overcomes P-glycoprotein-mediated multidrug-resistance via induction of apoptosis and oncosis in CEM-VLB 1000 cells. In: Experimental and Toxicologic Pathology. 2006 ; Vol. 58, No. 1. pp. 21-30.
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