Inhibiting the Expression of DNA Replication-Initiation Proteins Induces Apoptosis in Human Cancer Cells

Daorong Feng, Zheng Tu, Wenyan Wu, Chun Liang

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

DNA replication-initiation proteins are expressed in cancer cells, whereas some of these proteins are not expressed in nonproliferating normal cells. Therefore, replication-initiation proteins may present attractive targets for anticancer therapy. Using selected antisense oligodeoxynucleotides and small interfering RNA molecules targeted to the mRNA encoding the DNA replication-initiation proteins hCdc6p, hMcm2p, and hCdc45p, we show that the target genes could be effectively and specifically silenced and that, consequently, DNA replication and cell proliferation were inhibited in cultured human cells. In addition, silencing of these genes resulted in apoptosis in both p53-positive and -negative cancer cells but not in normal cells: cancer cells entered an abortive S-phase, whereas normal cells arrested mainly in G1 phase. Our studies are the first to suggest that inhibiting the expression of selective replication-initiation proteins is a novel and effective anticancer strategy.

Original languageEnglish (US)
Pages (from-to)7356-7364
Number of pages9
JournalCancer Research
Volume63
Issue number21
StatePublished - Nov 1 2003
Externally publishedYes

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DNA Replication
Apoptosis
Neoplasms
Proteins
Oligodeoxyribonucleotides
G1 Phase
Gene Silencing
S Phase
Small Interfering RNA
Cultured Cells
Cell Proliferation
Messenger RNA
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Inhibiting the Expression of DNA Replication-Initiation Proteins Induces Apoptosis in Human Cancer Cells. / Feng, Daorong; Tu, Zheng; Wu, Wenyan; Liang, Chun.

In: Cancer Research, Vol. 63, No. 21, 01.11.2003, p. 7356-7364.

Research output: Contribution to journalArticle

Feng, Daorong ; Tu, Zheng ; Wu, Wenyan ; Liang, Chun. / Inhibiting the Expression of DNA Replication-Initiation Proteins Induces Apoptosis in Human Cancer Cells. In: Cancer Research. 2003 ; Vol. 63, No. 21. pp. 7356-7364.
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