Pro-Apoptotic and Anti-Apoptotic Molecules Affecting Pathways of Signal Transduction

G. Kéri, G. Rácz, K. Magyar, L. Őrfi, A. Horváth, R. Schwab, B. B. Hegymegi, B. Szende

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Selective inhibition of the "false" proliferative signals via targeting tyrosine kinases resulting in the induction of apoptosis by depletion of the "survival factors" is one of the most studied and widely accepted concepts of modern chemotherapy. We have synthesized a series of potent tyrosine kinase inhibitors and tested these compounds for apoptosis induction. Some of the tyrosine kinase inhibitors caused either apoptotic or cytoplasmic vacuolar cell death in various tumor cell cultures. The somatostatin analogue oligopeptide TT-232, which indirectly inhibits tyrosine kinases, exerted a dose-dependent apoptosis-inducing effect. The tumor growth-inhibitory effect of TT-232 and some tyrosine kinase inhibitors has also been proven by in vivo experiments, using human tumor xenografts. On the other hand, a dose-dependent pro- or anti-apoptotic activity of (-)-deprenyl has been shown in melanoma cell cultures, the lower doses inhibiting and the higher doses inducing apoptosis. Various metabolites of (-)-deprenyl are responsible for these actions. The effect of (-)-deprenyl is connected with depolarization of mitochondrial membranes. The kinase inhibitors act on the growth factor receptor signaling pathways (survival factor pathways) and initiate the caspase cascade. The key enzyme for the action of both pro-apoptotic and anti-apoptotic compounds is caspase 3.

Original languageEnglish
Pages (from-to)109-112
Number of pages4
JournalAnnals of the New York Academy of Sciences
Volume1010
DOIs
Publication statusPublished - 2003

Fingerprint

Signal transduction
Protein-Tyrosine Kinases
Signal Transduction
Selegiline
Molecules
Tumors
Apoptosis
Cell culture
Cell Culture Techniques
Neoplasms
Oligopeptides
Apoptosis Regulatory Proteins
Chemotherapy
Growth Factor Receptors
Depolarization
Mitochondrial Membranes
Cell death
Caspases
Metabolites
Somatostatin

Keywords

  • AG-213
  • Apoptosis
  • Deprenyl
  • Signal transduction
  • TT-232

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Pro-Apoptotic and Anti-Apoptotic Molecules Affecting Pathways of Signal Transduction. / Kéri, G.; Rácz, G.; Magyar, K.; Őrfi, L.; Horváth, A.; Schwab, R.; Hegymegi, B. B.; Szende, B.

In: Annals of the New York Academy of Sciences, Vol. 1010, 2003, p. 109-112.

Research output: Contribution to journalArticle

@article{043980258343446da8d4e005062dc561,
title = "Pro-Apoptotic and Anti-Apoptotic Molecules Affecting Pathways of Signal Transduction",
abstract = "Selective inhibition of the {"}false{"} proliferative signals via targeting tyrosine kinases resulting in the induction of apoptosis by depletion of the {"}survival factors{"} is one of the most studied and widely accepted concepts of modern chemotherapy. We have synthesized a series of potent tyrosine kinase inhibitors and tested these compounds for apoptosis induction. Some of the tyrosine kinase inhibitors caused either apoptotic or cytoplasmic vacuolar cell death in various tumor cell cultures. The somatostatin analogue oligopeptide TT-232, which indirectly inhibits tyrosine kinases, exerted a dose-dependent apoptosis-inducing effect. The tumor growth-inhibitory effect of TT-232 and some tyrosine kinase inhibitors has also been proven by in vivo experiments, using human tumor xenografts. On the other hand, a dose-dependent pro- or anti-apoptotic activity of (-)-deprenyl has been shown in melanoma cell cultures, the lower doses inhibiting and the higher doses inducing apoptosis. Various metabolites of (-)-deprenyl are responsible for these actions. The effect of (-)-deprenyl is connected with depolarization of mitochondrial membranes. The kinase inhibitors act on the growth factor receptor signaling pathways (survival factor pathways) and initiate the caspase cascade. The key enzyme for the action of both pro-apoptotic and anti-apoptotic compounds is caspase 3.",
keywords = "AG-213, Apoptosis, Deprenyl, Signal transduction, TT-232",
author = "G. K{\'e}ri and G. R{\'a}cz and K. Magyar and L. Őrfi and A. Horv{\'a}th and R. Schwab and Hegymegi, {B. B.} and B. Szende",
year = "2003",
doi = "10.1196/annals.1299.018",
language = "English",
volume = "1010",
pages = "109--112",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Pro-Apoptotic and Anti-Apoptotic Molecules Affecting Pathways of Signal Transduction

AU - Kéri, G.

AU - Rácz, G.

AU - Magyar, K.

AU - Őrfi, L.

AU - Horváth, A.

AU - Schwab, R.

AU - Hegymegi, B. B.

AU - Szende, B.

PY - 2003

Y1 - 2003

N2 - Selective inhibition of the "false" proliferative signals via targeting tyrosine kinases resulting in the induction of apoptosis by depletion of the "survival factors" is one of the most studied and widely accepted concepts of modern chemotherapy. We have synthesized a series of potent tyrosine kinase inhibitors and tested these compounds for apoptosis induction. Some of the tyrosine kinase inhibitors caused either apoptotic or cytoplasmic vacuolar cell death in various tumor cell cultures. The somatostatin analogue oligopeptide TT-232, which indirectly inhibits tyrosine kinases, exerted a dose-dependent apoptosis-inducing effect. The tumor growth-inhibitory effect of TT-232 and some tyrosine kinase inhibitors has also been proven by in vivo experiments, using human tumor xenografts. On the other hand, a dose-dependent pro- or anti-apoptotic activity of (-)-deprenyl has been shown in melanoma cell cultures, the lower doses inhibiting and the higher doses inducing apoptosis. Various metabolites of (-)-deprenyl are responsible for these actions. The effect of (-)-deprenyl is connected with depolarization of mitochondrial membranes. The kinase inhibitors act on the growth factor receptor signaling pathways (survival factor pathways) and initiate the caspase cascade. The key enzyme for the action of both pro-apoptotic and anti-apoptotic compounds is caspase 3.

AB - Selective inhibition of the "false" proliferative signals via targeting tyrosine kinases resulting in the induction of apoptosis by depletion of the "survival factors" is one of the most studied and widely accepted concepts of modern chemotherapy. We have synthesized a series of potent tyrosine kinase inhibitors and tested these compounds for apoptosis induction. Some of the tyrosine kinase inhibitors caused either apoptotic or cytoplasmic vacuolar cell death in various tumor cell cultures. The somatostatin analogue oligopeptide TT-232, which indirectly inhibits tyrosine kinases, exerted a dose-dependent apoptosis-inducing effect. The tumor growth-inhibitory effect of TT-232 and some tyrosine kinase inhibitors has also been proven by in vivo experiments, using human tumor xenografts. On the other hand, a dose-dependent pro- or anti-apoptotic activity of (-)-deprenyl has been shown in melanoma cell cultures, the lower doses inhibiting and the higher doses inducing apoptosis. Various metabolites of (-)-deprenyl are responsible for these actions. The effect of (-)-deprenyl is connected with depolarization of mitochondrial membranes. The kinase inhibitors act on the growth factor receptor signaling pathways (survival factor pathways) and initiate the caspase cascade. The key enzyme for the action of both pro-apoptotic and anti-apoptotic compounds is caspase 3.

KW - AG-213

KW - Apoptosis

KW - Deprenyl

KW - Signal transduction

KW - TT-232

UR - http://www.scopus.com/inward/record.url?scp=1342284299&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1342284299&partnerID=8YFLogxK

U2 - 10.1196/annals.1299.018

DO - 10.1196/annals.1299.018

M3 - Article

VL - 1010

SP - 109

EP - 112

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -