Combined application of camptothecin and the guanylate cyclase activator YC-1: Impact on cell death and apoptosis-related proteins in ovarian carcinoma cell lines

Sun Joo Lee, Yun Jeong Kim, Chung Soo Lee, Jaeman Bae

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Camptothecin analogs and guanylate cyclase activator YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] have been shown to induce apoptosis in cancer cells. However, the combined effect of camptothecin analogs and YC-1 on the viability of epithelial ovarian cancer cells remains uncertain. We assessed the combined effect of YC-1 on the camptothecin toxicity in the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. Camptothecin and YC-1 induced apoptosis in OVCAR-3 and SK-OV-3 cells in a dose- and time-dependent manner. Both compounds induced nuclear damage, decreased Bid and Bcl-2 protein levels, enhanced cytochrome c release, activated caspase-3 and upregulated tumor suppressor p53. Camptothecin decreased Bax protein levels, whereas YC-1 increased Bax levels. YC-1 enhanced the camptothecin-induced changes in the apoptotic protein levels and increased apoptotic effect of camptothecin on ovarian carcinoma cell lines. The results suggested that YC-1 may enhance a camptothecin toxicity against ovarian carcinoma cell lines by increasing activation of the caspase-8 and Bid pathway as well as activation of the mitochondria-mediated apoptotic pathway, leading to cytochrome c release and subsequent caspase-3 activation. Combination of camptothecin analogs and YC-1 may provide a therapeutic benefit against ovarian adenocarcinoma.

Original languageEnglish
Pages (from-to)185-192
Number of pages8
JournalChemico-Biological Interactions
Volume181
Issue number2
DOIs
StatePublished - 2009 Oct 7

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Camptothecin
Guanylate Cyclase
Cell death
Cell Death
Cells
Apoptosis
Carcinoma
Cell Line
Proteins
Chemical activation
Cytochromes c
Caspase 3
Toxicity
Indazoles
bcl-2-Associated X Protein
Mitochondria
Caspase 8
Tumors
Neoplasms
Adenocarcinoma

Keywords

  • Apoptotic proteins
  • Camptothecin
  • Cell death
  • Epithelial ovarian cancer cell lines
  • YC-1

Cite this

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title = "Combined application of camptothecin and the guanylate cyclase activator YC-1: Impact on cell death and apoptosis-related proteins in ovarian carcinoma cell lines",
abstract = "Camptothecin analogs and guanylate cyclase activator YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] have been shown to induce apoptosis in cancer cells. However, the combined effect of camptothecin analogs and YC-1 on the viability of epithelial ovarian cancer cells remains uncertain. We assessed the combined effect of YC-1 on the camptothecin toxicity in the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. Camptothecin and YC-1 induced apoptosis in OVCAR-3 and SK-OV-3 cells in a dose- and time-dependent manner. Both compounds induced nuclear damage, decreased Bid and Bcl-2 protein levels, enhanced cytochrome c release, activated caspase-3 and upregulated tumor suppressor p53. Camptothecin decreased Bax protein levels, whereas YC-1 increased Bax levels. YC-1 enhanced the camptothecin-induced changes in the apoptotic protein levels and increased apoptotic effect of camptothecin on ovarian carcinoma cell lines. The results suggested that YC-1 may enhance a camptothecin toxicity against ovarian carcinoma cell lines by increasing activation of the caspase-8 and Bid pathway as well as activation of the mitochondria-mediated apoptotic pathway, leading to cytochrome c release and subsequent caspase-3 activation. Combination of camptothecin analogs and YC-1 may provide a therapeutic benefit against ovarian adenocarcinoma.",
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Combined application of camptothecin and the guanylate cyclase activator YC-1 : Impact on cell death and apoptosis-related proteins in ovarian carcinoma cell lines. / Lee, Sun Joo; Kim, Yun Jeong; Lee, Chung Soo; Bae, Jaeman.

In: Chemico-Biological Interactions, Vol. 181, No. 2, 07.10.2009, p. 185-192.

Research output: Contribution to journalArticle

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