Potent induction of apoptosis in human hepatoma cell lines by targeted cytotoxic somatostatin analogue AN-238

Malika Lasfer, Nathalie Vadrot, Andrew V Schally, Attila Nagy, Gabor Halmos, Dominique Pessayre, Gérard Feldmann, Florence J. Reyl-Desmars

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The efficacy of a targeted cytotoxic hybrid somatostatin analogue AN-238 and of its superactive radical 2-pyrrolinodoxorubicin (AN-201) to induce apoptosis of HepG2 and Hep3B human hepatoma cell lines were studied. AN-238 was designed to selectively target tumor cells expressing somatostatin receptor subtypes (ssts). Its effects on HepG2 or Hep3B cells displaying or lacking tumor suppressor p53, respectively, were compared. Normal rat isolated hepatocytes were also tested. ssts were characterized by binding assays and RT-PCR. Cytotoxicity was quantified by flow cytometry. DNA fragmentation was studied by gel electrophoresis, PARP cleavage by Western blot and ROS formation using fluorescent probes. Specific binding of iodinated RC-160 to HepG2 and Hep3B cells, and its displacement by AN-238 was characterized. mRNA for hsst2A was found in both cell lines. Flow cytometry showed a stronger effect of AN-238 than AN-201 to induce sub-G1 phase. DNA fragmentation, nuclear bodies, and PARP cleavage were observed. In addition, AN-238 increased formation of ROS more potently than AN-201. However, no inductions of DNA fragmentation by AN-201 or AN-238 were observed on rat hepatocytes. Our results indicate that, in liver cancer, the cytotoxic somatostatin analogue AN-238 is a powerful agent that can induce apoptosis, through ssts and independently of p53.

Original languageEnglish
Pages (from-to)230-237
Number of pages8
JournalJournal of Hepatology
Volume42
Issue number2
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

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Somatostatin
Hepatocellular Carcinoma
Apoptosis
Cell Line
Somatostatin Receptors
DNA Fragmentation
Hepatocytes
Flow Cytometry
Hep G2 Cells
G1 Phase
Liver Neoplasms
AN 238
Fluorescent Dyes
Electrophoresis
Neoplasms
Western Blotting
Gels
AN 204
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Cell death
  • Chemotherapeutic drugs
  • Hepatocellular carcinoma
  • Hybrid compounds
  • Receptors
  • Tumor targeting

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Potent induction of apoptosis in human hepatoma cell lines by targeted cytotoxic somatostatin analogue AN-238. / Lasfer, Malika; Vadrot, Nathalie; Schally, Andrew V; Nagy, Attila; Halmos, Gabor; Pessayre, Dominique; Feldmann, Gérard; Reyl-Desmars, Florence J.

In: Journal of Hepatology, Vol. 42, No. 2, 01.02.2005, p. 230-237.

Research output: Contribution to journalArticle

Lasfer, M, Vadrot, N, Schally, AV, Nagy, A, Halmos, G, Pessayre, D, Feldmann, G & Reyl-Desmars, FJ 2005, 'Potent induction of apoptosis in human hepatoma cell lines by targeted cytotoxic somatostatin analogue AN-238', Journal of Hepatology, vol. 42, no. 2, pp. 230-237. https://doi.org/10.1016/j.jhep.2004.10.014
Lasfer, Malika ; Vadrot, Nathalie ; Schally, Andrew V ; Nagy, Attila ; Halmos, Gabor ; Pessayre, Dominique ; Feldmann, Gérard ; Reyl-Desmars, Florence J. / Potent induction of apoptosis in human hepatoma cell lines by targeted cytotoxic somatostatin analogue AN-238. In: Journal of Hepatology. 2005 ; Vol. 42, No. 2. pp. 230-237.
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