Antiproliferative activity induced by the somatostatin analogue, TT-232, in human pancreatic cancer cells

J. U. Lee, R. Hosotani, M. Wada, R. Doi, T. Koshiba, K. Fujimoto, Y. Miyamoto, Shoichiro Tsuji, S. Nakajima, M. Hirohashi, T. Uehara, Y. Arano, N. Fujii, M. Imamura

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Somatostatin analogues have been developed as antiproliferative agents, but their administration as general antitumour agents is limited, mainly because of the wide distribution of somatostatin receptors throughout the human body. TT-232, a new somatostatin structural analogue, was reported to have tumour-selective antiproliferative activity without an antisecretory action. We examined whether TT-232 had antiproliferative activity in human pancreatic cancer cell lines, and compared its antiproliferative activity with that of RC-160 and other TT-232 derivatives. TT-232 inhibited the growth of all of the cell lines used in this study and induced apoptotic cell death. RC-160 showed no such growth inhibition. TT-232 also inhibited tumour formation in a xenograft model. A competitive binding assay was performed using the cell membrane fraction and 111In-DTPA-TT-232 in order to show the existence of a specific binding site on the cells. A specific binding site was detected in MIAPaCa-2 cells. It has been shown that the activation of protein tyrosine phosphatase (PTPase) is one of the main intracellular pathways responsible for somatostatinergic inhibition of cell growth. We found a significant PTPase stimulation after TT-232 administration using an immunoblot analysis assessing the level of protein tyrosine phosphorylation, and also a direct measurement of the PTPase activity. We also demonstrated that PTPase stimulation by TT-232 was involved in its antiproliferative activity as this activity was reversed by the addition of sodium orthovanadate, a PTPase inhibitor. Our results indicate that TT-232 could be a potentially useful therapeutic agent if these data are translated into clinical practice.

Original languageEnglish
Pages (from-to)1526-1534
Number of pages9
JournalEuropean Journal of Cancer
Volume38
Issue number11
DOIs
Publication statusPublished - 22-07-2002

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Somatostatin
Pancreatic Neoplasms
Protein Tyrosine Phosphatases
Growth
Binding Sites
TT2-32
Cell Line
Somatostatin Receptors
Pentetic Acid
Competitive Binding
Vanadates
Human Body
Heterografts
Human Activities
Antineoplastic Agents
Tyrosine
Neoplasms
Cell Death
Sodium
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lee, J. U., Hosotani, R., Wada, M., Doi, R., Koshiba, T., Fujimoto, K., ... Imamura, M. (2002). Antiproliferative activity induced by the somatostatin analogue, TT-232, in human pancreatic cancer cells. European Journal of Cancer, 38(11), 1526-1534. https://doi.org/10.1016/S0959-8049(02)00101-6
Lee, J. U. ; Hosotani, R. ; Wada, M. ; Doi, R. ; Koshiba, T. ; Fujimoto, K. ; Miyamoto, Y. ; Tsuji, Shoichiro ; Nakajima, S. ; Hirohashi, M. ; Uehara, T. ; Arano, Y. ; Fujii, N. ; Imamura, M. / Antiproliferative activity induced by the somatostatin analogue, TT-232, in human pancreatic cancer cells. In: European Journal of Cancer. 2002 ; Vol. 38, No. 11. pp. 1526-1534.
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Lee, JU, Hosotani, R, Wada, M, Doi, R, Koshiba, T, Fujimoto, K, Miyamoto, Y, Tsuji, S, Nakajima, S, Hirohashi, M, Uehara, T, Arano, Y, Fujii, N & Imamura, M 2002, 'Antiproliferative activity induced by the somatostatin analogue, TT-232, in human pancreatic cancer cells', European Journal of Cancer, vol. 38, no. 11, pp. 1526-1534. https://doi.org/10.1016/S0959-8049(02)00101-6

Antiproliferative activity induced by the somatostatin analogue, TT-232, in human pancreatic cancer cells. / Lee, J. U.; Hosotani, R.; Wada, M.; Doi, R.; Koshiba, T.; Fujimoto, K.; Miyamoto, Y.; Tsuji, Shoichiro; Nakajima, S.; Hirohashi, M.; Uehara, T.; Arano, Y.; Fujii, N.; Imamura, M.

In: European Journal of Cancer, Vol. 38, No. 11, 22.07.2002, p. 1526-1534.

Research output: Contribution to journalArticle

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T1 - Antiproliferative activity induced by the somatostatin analogue, TT-232, in human pancreatic cancer cells

AU - Lee, J. U.

AU - Hosotani, R.

AU - Wada, M.

AU - Doi, R.

AU - Koshiba, T.

AU - Fujimoto, K.

AU - Miyamoto, Y.

AU - Tsuji, Shoichiro

AU - Nakajima, S.

AU - Hirohashi, M.

AU - Uehara, T.

AU - Arano, Y.

AU - Fujii, N.

AU - Imamura, M.

PY - 2002/7/22

Y1 - 2002/7/22

N2 - Somatostatin analogues have been developed as antiproliferative agents, but their administration as general antitumour agents is limited, mainly because of the wide distribution of somatostatin receptors throughout the human body. TT-232, a new somatostatin structural analogue, was reported to have tumour-selective antiproliferative activity without an antisecretory action. We examined whether TT-232 had antiproliferative activity in human pancreatic cancer cell lines, and compared its antiproliferative activity with that of RC-160 and other TT-232 derivatives. TT-232 inhibited the growth of all of the cell lines used in this study and induced apoptotic cell death. RC-160 showed no such growth inhibition. TT-232 also inhibited tumour formation in a xenograft model. A competitive binding assay was performed using the cell membrane fraction and 111In-DTPA-TT-232 in order to show the existence of a specific binding site on the cells. A specific binding site was detected in MIAPaCa-2 cells. It has been shown that the activation of protein tyrosine phosphatase (PTPase) is one of the main intracellular pathways responsible for somatostatinergic inhibition of cell growth. We found a significant PTPase stimulation after TT-232 administration using an immunoblot analysis assessing the level of protein tyrosine phosphorylation, and also a direct measurement of the PTPase activity. We also demonstrated that PTPase stimulation by TT-232 was involved in its antiproliferative activity as this activity was reversed by the addition of sodium orthovanadate, a PTPase inhibitor. Our results indicate that TT-232 could be a potentially useful therapeutic agent if these data are translated into clinical practice.

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