Role of Bcl-2 family proteins and caspase-3 in sanguinarine-induced bimodal cell death

P. Weerasinghe, S. Hallock, Shou-Ching Tang, A. Liepins

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Sanguinarine, a benzophenanthridine alkaloid, has anticancer potential through induction of cell death. We previously demonstrated that sanguinarine treatment at a low level induced apoptosis or programmed cell death (PCD) in the Bcl-2 low-expressing K562 human erythroleukemia cells, and that a high level induced blister cell death (BCD); whereas Bcl-2 overexpressing, sanguinarine-treated JM1 pre-B lymphoblastic cells displayed neither apoptosis nor BCD morphologies. Here, we report that sanguinarine-treated K562 cells, when analyzed by western blot, showed significant increase in expression of the pro-apoptotic Bax protein in apoptosis, but not in BCD. cDNA expression array of PCD in K562 cells failed to reveal the presence of Bax at the gene transcript level, which suggests that this cell death process does not require de novo protein synthesis. Treated JM1 cells, on the other hand, showed an increase in the expression of Bcl-2 protein in both forms of cell death, but failed to show Bax expression. The role of other members of the Bcl-2 family remained negligible. Caspase-3 activation was observed in apoptosis of K562 cells but not in BCD or in sanguinarine-treated JM1 cells. These results suggest that sanguinarine in K562 cells induces apoptosis through increasing Bax and activating caspase-3, whereas sanguinarine-induced BCD involves neither. These results also suggest that in JM1 cells, Bcl-2 may play a role in susceptibility of cells to induction of apoptosis and BCD.

Original languageEnglish (US)
Pages (from-to)371-381
Number of pages11
JournalCell Biology and Toxicology
Volume17
Issue number6
DOIs
StatePublished - Dec 1 2001

Fingerprint

Cell death
Caspase 3
Cell Death
Blister
K562 Cells
Proteins
Apoptosis
Benzophenanthridines
sanguinarine
bcl-2-Associated X Protein
Leukemia, Erythroblastic, Acute
Apoptosis Regulatory Proteins
B-Lymphoid Precursor Cells
Oligonucleotide Array Sequence Analysis
Alkaloids
Complementary DNA
Genes
Western Blotting
Chemical activation

Keywords

  • Apoptosis
  • Bax
  • Bcl-2
  • Blebbing
  • Chemoresistance
  • Sanguinarine

ASJC Scopus subject areas

  • Toxicology
  • Cell Biology
  • Health, Toxicology and Mutagenesis

Cite this

Role of Bcl-2 family proteins and caspase-3 in sanguinarine-induced bimodal cell death. / Weerasinghe, P.; Hallock, S.; Tang, Shou-Ching; Liepins, A.

In: Cell Biology and Toxicology, Vol. 17, No. 6, 01.12.2001, p. 371-381.

Research output: Contribution to journalArticle

Weerasinghe, P. ; Hallock, S. ; Tang, Shou-Ching ; Liepins, A. / Role of Bcl-2 family proteins and caspase-3 in sanguinarine-induced bimodal cell death. In: Cell Biology and Toxicology. 2001 ; Vol. 17, No. 6. pp. 371-381.
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