A class of DNA-binding peptides from wheat bud causes growth inhibition, G2 cell cycle arrest and apoptosis induction in HeLa cells.
BACKGROUND
Deproteinized DNA from eukaryotic and prokaryotic cells still contains a low-molecular weight peptidic fraction which can be dissociated by alkalinization of the medium. This fraction inhibits RNA transcription and tumor cell growth. Removal from DNA of normal cells causes amplification of DNA template activity. This effect is lower or absent in several cancer cell lines. Likewise, the amount of active peptides in cancer cell DNA extracts is lower than in DNA preparation of the corresponding normal cells. Such evidence, and their ubiquitous presence, suggests that they are a regulatory, conserved factor involved in the control of normal cell growth and gene expression.


RESULTS
We report that peptides extracted from wheat bud chromatin induce growth inhibition, G2 arrest and caspase-dependent apoptosis in HeLa cells. The growth rate is decreased in cells treated during the S phase only and it is accompanied by DNA damage and DNA synthesis inhibition. In G2 cells, this treatment induces inactivation of the CDK1-cyclin B1 complex and an increase of active chk1 kinase expression.


CONCLUSIONS
The data indicate that the chromatin peptidic pool inhibits HeLa cell growth by causing defective DNA replication which, in turn, arrests cell cycle progression to mitosis via G2 checkpoint pathway activation.
Mancinelli
Loretta
L
Department of Cellular and Environmental Biology, CEMIN (Center of Excellence on Innovative Nanostructured Materials for chemical, physical and biomedical applications), University of Perugia, Perugia, Italy. loretta@unipg.it
De Angelis
Paula M
PM
Annulli
Lucia
L
Padovini
Valentina
V
Elgjo
Kjell
K
Gianfranceschi
Gian Luigi
GL
D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D048708:Cell Growth Processes / Q000187:drug effects; D002843:Chromatin / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D004249:DNA Damage / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D010940:Plant Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects; D014908:Triticum / Q000737:chemistry*
C534699:CCNB1 protein, human; D002843:Chromatin; D019926:Cyclin B; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D010455:Peptides; D010940:Plant Proteins; D016203:CDC2 Protein Kinase