Increased local vascular endothelial growth factor expression associated with antitumor activity of proteasome inhibitor

T. Stokłosa, J. Goła̧b, Cezary Wojcik, P. Włodarski, A. Jalili, P. Januszko, A. Giermasz, G. M. Wilczyński, E. Pleban, M. Marczak, S. Wilk, M. Jakóbisiak

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Inhibition of the proteasome, a multicatalytic proteinase complex, is an attractive approach to cancer therapy. Here we report that a selective inhibitor of the chymotrypsin-like activity of the proteasome, PSI (N-benzyloxycarbonyl- IIe-Glu(O-t-butyl)-Ala-leucinal) may inhibit growth of solid tumors not only through apoptosis induction, but also indirectly - through inhibition of angiogenesis. Two murine tumors: colon adenocarcinoma (C-26) and Lewis lung carcinoma (3LL) were chosen to study the antitumor effect of PSI. In an in vivo model of local tumor growth, PSI exerted significant antitumor effects against C-26 colon carcinoma, but not against 3LL lung carcinoma. Retardation of tumor growth was observed in mice treated with both 10 nmoles and 100 nmoles doses of PSI and in the latter group prolongation of the survival time of tumor-bearing mice was observed. PSI inhibited angiogenesis in the C-26 growing tumors with no such effect in 3LL tumors. Unexpectedly, that activity was associated with upregulation of vascular endothelial growth factor (VEGF) at the level of mRNA expression and protein production in C-26 tumors treated with PSI. C-26 cells treated with PSI produced increased amounts of VEGF in vitro in a dose-and time-dependent manner. We demonstrated that in C-26 colon adenocarcionoma higher VEGF production may render endothelial cells susceptible to the proapoptotic activity of PSI and is associated with inhibition of tumor growth.

Original languageEnglish (US)
Pages (from-to)193-204
Number of pages12
JournalApoptosis
Volume9
Issue number2
DOIs
StatePublished - Mar 2004
Externally publishedYes

Fingerprint

Proteasome Inhibitors
Vascular Endothelial Growth Factor A
Tumors
Neoplasms
Proteasome Endopeptidase Complex
Colon
Growth
Bearings (structural)
Lewis Lung Carcinoma
Carcinoma
Endothelial cells
Chymotrypsin
Adenocarcinoma
Up-Regulation
Endothelial Cells
Apoptosis
Messenger RNA
Lung

Keywords

  • Angiogenesis
  • Apoptosis
  • Cancer therapy
  • Proteasome
  • VEGF

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

Increased local vascular endothelial growth factor expression associated with antitumor activity of proteasome inhibitor. / Stokłosa, T.; Goła̧b, J.; Wojcik, Cezary; Włodarski, P.; Jalili, A.; Januszko, P.; Giermasz, A.; Wilczyński, G. M.; Pleban, E.; Marczak, M.; Wilk, S.; Jakóbisiak, M.

In: Apoptosis, Vol. 9, No. 2, 03.2004, p. 193-204.

Research output: Contribution to journalArticle

Stokłosa, T, Goła̧b, J, Wojcik, C, Włodarski, P, Jalili, A, Januszko, P, Giermasz, A, Wilczyński, GM, Pleban, E, Marczak, M, Wilk, S & Jakóbisiak, M 2004, 'Increased local vascular endothelial growth factor expression associated with antitumor activity of proteasome inhibitor', Apoptosis, vol. 9, no. 2, pp. 193-204. https://doi.org/10.1023/B:APPT.0000018801.59062.1d
Stokłosa, T. ; Goła̧b, J. ; Wojcik, Cezary ; Włodarski, P. ; Jalili, A. ; Januszko, P. ; Giermasz, A. ; Wilczyński, G. M. ; Pleban, E. ; Marczak, M. ; Wilk, S. ; Jakóbisiak, M. / Increased local vascular endothelial growth factor expression associated with antitumor activity of proteasome inhibitor. In: Apoptosis. 2004 ; Vol. 9, No. 2. pp. 193-204.
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AU - Jalili, A.

AU - Januszko, P.

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