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The effect of chelerythrine on cell growth, apoptosis, and cell cycle in human normal and cancer cells in comparison with sanguinarine

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Abstract

We compared the effects of chelerythrine (CHE) and sanguinarine (SA) on human prostate cancer cell lines (LNCaP and DU-145) and primary culture of human gingival fibroblasts. CHE and SA treatment of cell lines for 24 h resulted in (1) inhibition of cell viability in a dose-dependent manner in all tested cells (as evaluated by MTT test and bromodeoxyuridine incorporation assay); (2) dose-dependent increase in DNA damage in all tested cells (as evaluated by DNA comet assay); (3) changes in apoptosis (assessed by western blot analysis and TUNEL assay); and (4) significant induction of cyclin kinase inhibitors p21Waf1/Cip1 and p27Kip1 in prostate cancer cells (identified by western blot analysis). Our study demonstrates that CHE had significant cytotoxic effect, independent of p53 and androgen status, on human prostate cancer cell lines. Normal gingival fibroblasts and DU-145 cells were more sensitive to the treatment with both alkaloids than were LNCaP cells. CHE and SA may be prospective natural molecules for use in the treatment of prostate cancer owing to their involvement in apoptosis and cell cycle regulation.

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Abbreviations

AR:

androgen receptor

BrdU:

bromodeoxyuridine

CC:

column chromatography

cdk:

cyclin-dependent kinase

CHE:

chelerythrine

DAPI:

4′,6-diamidino-2-phenylindole

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

dimethyl sulfoxide

FCS:

fetal calf serum

FITC:

fluorescein isothiocyanate

MTT:

3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide

NF-κB:

nuclear factor kappa B

PARP:

poly-(ADP-ribose) polymerase

PBS:

phosphate-buffered saline

PCNA:

proliferating-cell nuclear antigen

PSA:

prostate-specific antigen

QBA:

quaternary benzo[c]phenanthridine alkaloids

Rb:

retinoblastoma gene

SA:

sanguinarine

TUNEL:

terminal deoxynucleotide transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling

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Authors and Affiliations

  1. Laboratory of Molecular Pathology, Institute of Pathology, Faculty of Medicine, Palacký University, Hněvotínská 3, 77515, Olomouc, Czech Republic

    J. Malíková & A. Hlobilková

  2. Department of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacký University, Olomouc, Czech Republic

    A. Zdařilová & J. Ulrichová

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  1. J. Malíková
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  2. A. Zdařilová
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  3. A. Hlobilková
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  4. J. Ulrichová
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Correspondence to J. Malíková.

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Malíková, J., Zdařilová, A., Hlobilková, A. et al. The effect of chelerythrine on cell growth, apoptosis, and cell cycle in human normal and cancer cells in comparison with sanguinarine. Cell Biol Toxicol 22, 439–453 (2006). https://doi.org/10.1007/s10565-006-0109-x

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  • DOI: https://doi.org/10.1007/s10565-006-0109-x

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