Effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y human neuroblastoma cells

Annika M. Jalava, Jari Heikkilä, Göran Åkerlind, George Pettit, Karl E O Åkerman

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

SH-SY5Y human neuroblastoma cells can be induced to differentiate to mature ganglion cells when treated with the phorbol ester tetradecanoylphorbol acetate (TPA). Bryostatins are a new class of protein kinase C activators that are structurally unrelated to phorbol esters. This paper describes the effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y cells. Both bryostatins induced a rapid translocation of protein kinase C from the cytosol to the membrane fraction. Within 24 h, the bryostatins had caused a nearly complete down-regulation of the enzyme. Bryostatin 1 competed for [3H]phorbol-12,13-dibutyrate binding in intact cells with potency equal to that of TPA, in contrast to bryostatin 2, which exhibited a Ki value 1 order of magnitude higher than those of the two other agents. Bryostatins induced morphological changes similar to those induced by TPA. These changes were, however, only transient, occurring during the first 6 h of incubation in the presence of these compounds. By 72 h, the cells had acquired a morphology typical of untreated cells and, although a wide range of bryostatin concentrations were used, morphological changes characteristic of differentiated SH-SY5Y cells were not detected at 72 h. Bryostatin 1 at 5 nM and bryostatin 2 at 100 nM inhibited DNA synthesis, as measured by incorporation of [3H]thymidine by SH-SY5Y cells, although to a significantly lesser degree than TPA. In spite of the fact that bryostatins failed to induce morphological differentiation in SH-SY5Y cells, these compounds down-regulated c-myc mRNA expression. Bryostatins were significantly weaker in stimulating noradrenaline synthesis, compared with TPA, and high concentrations of these agents blocked the effect of the phorbol ester when they were included together with TPA. When SH-SY5Y cells were incubated in the presence of high concentrations of bryostatins, a decreased sensitivity of cells to muscarinic agonist-induced increases in cytosolic free Ca2+ was observed. The results suggest that down-regulation of protein kinase C activity and c-myc mRNA expression do not necessarily correlate with the morphological differentiation of SH-SY5Y cells.

Original languageEnglish (US)
Pages (from-to)3422-3428
Number of pages7
JournalCancer Research
Volume50
Issue number11
StatePublished - Jun 1 1990

Fingerprint

Bryostatins
Neuroblastoma
Tetradecanoylphorbol Acetate
Phorbol Esters
Protein Kinase C
bryostatin 1
bryostatin 2
Down-Regulation
Phorbol 12,13-Dibutyrate
Muscarinic Agonists
Messenger RNA
Ganglia
Cytosol
Thymidine
Norepinephrine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Jalava, A. M., Heikkilä, J., Åkerlind, G., Pettit, G., & Åkerman, K. E. O. (1990). Effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y human neuroblastoma cells. Cancer Research, 50(11), 3422-3428.

Effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y human neuroblastoma cells. / Jalava, Annika M.; Heikkilä, Jari; Åkerlind, Göran; Pettit, George; Åkerman, Karl E O.

In: Cancer Research, Vol. 50, No. 11, 01.06.1990, p. 3422-3428.

Research output: Contribution to journalArticle

Jalava, AM, Heikkilä, J, Åkerlind, G, Pettit, G & Åkerman, KEO 1990, 'Effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y human neuroblastoma cells', Cancer Research, vol. 50, no. 11, pp. 3422-3428.
Jalava, Annika M. ; Heikkilä, Jari ; Åkerlind, Göran ; Pettit, George ; Åkerman, Karl E O. / Effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y human neuroblastoma cells. In: Cancer Research. 1990 ; Vol. 50, No. 11. pp. 3422-3428.
@article{0478bbab414447019867efedbe672cf9,
title = "Effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y human neuroblastoma cells",
abstract = "SH-SY5Y human neuroblastoma cells can be induced to differentiate to mature ganglion cells when treated with the phorbol ester tetradecanoylphorbol acetate (TPA). Bryostatins are a new class of protein kinase C activators that are structurally unrelated to phorbol esters. This paper describes the effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y cells. Both bryostatins induced a rapid translocation of protein kinase C from the cytosol to the membrane fraction. Within 24 h, the bryostatins had caused a nearly complete down-regulation of the enzyme. Bryostatin 1 competed for [3H]phorbol-12,13-dibutyrate binding in intact cells with potency equal to that of TPA, in contrast to bryostatin 2, which exhibited a Ki value 1 order of magnitude higher than those of the two other agents. Bryostatins induced morphological changes similar to those induced by TPA. These changes were, however, only transient, occurring during the first 6 h of incubation in the presence of these compounds. By 72 h, the cells had acquired a morphology typical of untreated cells and, although a wide range of bryostatin concentrations were used, morphological changes characteristic of differentiated SH-SY5Y cells were not detected at 72 h. Bryostatin 1 at 5 nM and bryostatin 2 at 100 nM inhibited DNA synthesis, as measured by incorporation of [3H]thymidine by SH-SY5Y cells, although to a significantly lesser degree than TPA. In spite of the fact that bryostatins failed to induce morphological differentiation in SH-SY5Y cells, these compounds down-regulated c-myc mRNA expression. Bryostatins were significantly weaker in stimulating noradrenaline synthesis, compared with TPA, and high concentrations of these agents blocked the effect of the phorbol ester when they were included together with TPA. When SH-SY5Y cells were incubated in the presence of high concentrations of bryostatins, a decreased sensitivity of cells to muscarinic agonist-induced increases in cytosolic free Ca2+ was observed. The results suggest that down-regulation of protein kinase C activity and c-myc mRNA expression do not necessarily correlate with the morphological differentiation of SH-SY5Y cells.",
author = "Jalava, {Annika M.} and Jari Heikkil{\"a} and G{\"o}ran {\AA}kerlind and George Pettit and {\AA}kerman, {Karl E O}",
year = "1990",
month = "6",
day = "1",
language = "English (US)",
volume = "50",
pages = "3422--3428",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y human neuroblastoma cells

AU - Jalava, Annika M.

AU - Heikkilä, Jari

AU - Åkerlind, Göran

AU - Pettit, George

AU - Åkerman, Karl E O

PY - 1990/6/1

Y1 - 1990/6/1

N2 - SH-SY5Y human neuroblastoma cells can be induced to differentiate to mature ganglion cells when treated with the phorbol ester tetradecanoylphorbol acetate (TPA). Bryostatins are a new class of protein kinase C activators that are structurally unrelated to phorbol esters. This paper describes the effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y cells. Both bryostatins induced a rapid translocation of protein kinase C from the cytosol to the membrane fraction. Within 24 h, the bryostatins had caused a nearly complete down-regulation of the enzyme. Bryostatin 1 competed for [3H]phorbol-12,13-dibutyrate binding in intact cells with potency equal to that of TPA, in contrast to bryostatin 2, which exhibited a Ki value 1 order of magnitude higher than those of the two other agents. Bryostatins induced morphological changes similar to those induced by TPA. These changes were, however, only transient, occurring during the first 6 h of incubation in the presence of these compounds. By 72 h, the cells had acquired a morphology typical of untreated cells and, although a wide range of bryostatin concentrations were used, morphological changes characteristic of differentiated SH-SY5Y cells were not detected at 72 h. Bryostatin 1 at 5 nM and bryostatin 2 at 100 nM inhibited DNA synthesis, as measured by incorporation of [3H]thymidine by SH-SY5Y cells, although to a significantly lesser degree than TPA. In spite of the fact that bryostatins failed to induce morphological differentiation in SH-SY5Y cells, these compounds down-regulated c-myc mRNA expression. Bryostatins were significantly weaker in stimulating noradrenaline synthesis, compared with TPA, and high concentrations of these agents blocked the effect of the phorbol ester when they were included together with TPA. When SH-SY5Y cells were incubated in the presence of high concentrations of bryostatins, a decreased sensitivity of cells to muscarinic agonist-induced increases in cytosolic free Ca2+ was observed. The results suggest that down-regulation of protein kinase C activity and c-myc mRNA expression do not necessarily correlate with the morphological differentiation of SH-SY5Y cells.

AB - SH-SY5Y human neuroblastoma cells can be induced to differentiate to mature ganglion cells when treated with the phorbol ester tetradecanoylphorbol acetate (TPA). Bryostatins are a new class of protein kinase C activators that are structurally unrelated to phorbol esters. This paper describes the effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y cells. Both bryostatins induced a rapid translocation of protein kinase C from the cytosol to the membrane fraction. Within 24 h, the bryostatins had caused a nearly complete down-regulation of the enzyme. Bryostatin 1 competed for [3H]phorbol-12,13-dibutyrate binding in intact cells with potency equal to that of TPA, in contrast to bryostatin 2, which exhibited a Ki value 1 order of magnitude higher than those of the two other agents. Bryostatins induced morphological changes similar to those induced by TPA. These changes were, however, only transient, occurring during the first 6 h of incubation in the presence of these compounds. By 72 h, the cells had acquired a morphology typical of untreated cells and, although a wide range of bryostatin concentrations were used, morphological changes characteristic of differentiated SH-SY5Y cells were not detected at 72 h. Bryostatin 1 at 5 nM and bryostatin 2 at 100 nM inhibited DNA synthesis, as measured by incorporation of [3H]thymidine by SH-SY5Y cells, although to a significantly lesser degree than TPA. In spite of the fact that bryostatins failed to induce morphological differentiation in SH-SY5Y cells, these compounds down-regulated c-myc mRNA expression. Bryostatins were significantly weaker in stimulating noradrenaline synthesis, compared with TPA, and high concentrations of these agents blocked the effect of the phorbol ester when they were included together with TPA. When SH-SY5Y cells were incubated in the presence of high concentrations of bryostatins, a decreased sensitivity of cells to muscarinic agonist-induced increases in cytosolic free Ca2+ was observed. The results suggest that down-regulation of protein kinase C activity and c-myc mRNA expression do not necessarily correlate with the morphological differentiation of SH-SY5Y cells.

UR - http://www.scopus.com/inward/record.url?scp=0025314944&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025314944&partnerID=8YFLogxK

M3 - Article

VL - 50

SP - 3422

EP - 3428

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 11

ER -