Inhibition of cyclin D1 expression and induction of apoptosis by inostamycin in small cell lung carcinoma cells

Masaya Imoto, Keiko Tanabe, Siro Simizu, Etsu Tashiro, Minoru Takada, Kazuo Umezawa

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Previously, we demonstrated that inostamycin, an inhibitor of phosphatidylinositol turnover, caused cell cycle arrest at the G1 phase, inhibiting the expression of cyclins D1 and E in normal cells. In the present study, we examined the effects of inostamycin on cell cycle progression and apoptosis in human small cell lung carcinoma Ms-1 cells. Treatment of exponentially proliferating Ms-1 cells with low concentrations of inostamycin caused cells to accumulate in the G1 phase. We found that inostamycin decreased cyclin D, and increased cyclin-dependent kinase inhibitors such as p21(WAF1) and p27(KIP1) in Ms-1 cells. On the other hand, higher concentrations of inostamycin induced morphological apoptosis and DNA fragmentation in Ms-1 cells without affecting the expression of p53, Bcl-2 and Bax. Inostamycin-induced apoptosis was suppressed by an inhibitor of caspase-3, and a 17 kDa fragment of activated caspase-3 was detected following inostamycin treatment. Therefore, caspase-3(-like) would appear to be involved in inostamycin-induced apoptosis. On the other hand, an inhibitor of caspase-3(-like) proteases did not affect the inhibitory effect of inostamycin on cyclin D1 expression, suggesting that caspase-3(-like) proteases were not responsible for inostamycin-induced G1 arrest.

Original languageEnglish
Pages (from-to)315-322
Number of pages8
JournalJapanese Journal of Cancer Research
Volume89
Issue number3
Publication statusPublished - 1998 Mar

Fingerprint

Cyclin D1
Small Cell Lung Carcinoma
Apoptosis
Caspase 3
G1 Phase
Peptide Hydrolases
inostamycin
Cyclin D
Cyclin E
Cyclin-Dependent Kinases
DNA Fragmentation
Phosphatidylinositols
Cell Cycle Checkpoints
Cell Cycle

Keywords

  • Caspase-3
  • Cyclin D1
  • Inostomycin
  • p27(KIP1)

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Inhibition of cyclin D1 expression and induction of apoptosis by inostamycin in small cell lung carcinoma cells. / Imoto, Masaya; Tanabe, Keiko; Simizu, Siro; Tashiro, Etsu; Takada, Minoru; Umezawa, Kazuo.

In: Japanese Journal of Cancer Research, Vol. 89, No. 3, 03.1998, p. 315-322.

Research output: Contribution to journalArticle

@article{d34c7dbabbe94363b1cf9bc0625c9bee,
title = "Inhibition of cyclin D1 expression and induction of apoptosis by inostamycin in small cell lung carcinoma cells",
abstract = "Previously, we demonstrated that inostamycin, an inhibitor of phosphatidylinositol turnover, caused cell cycle arrest at the G1 phase, inhibiting the expression of cyclins D1 and E in normal cells. In the present study, we examined the effects of inostamycin on cell cycle progression and apoptosis in human small cell lung carcinoma Ms-1 cells. Treatment of exponentially proliferating Ms-1 cells with low concentrations of inostamycin caused cells to accumulate in the G1 phase. We found that inostamycin decreased cyclin D, and increased cyclin-dependent kinase inhibitors such as p21(WAF1) and p27(KIP1) in Ms-1 cells. On the other hand, higher concentrations of inostamycin induced morphological apoptosis and DNA fragmentation in Ms-1 cells without affecting the expression of p53, Bcl-2 and Bax. Inostamycin-induced apoptosis was suppressed by an inhibitor of caspase-3, and a 17 kDa fragment of activated caspase-3 was detected following inostamycin treatment. Therefore, caspase-3(-like) would appear to be involved in inostamycin-induced apoptosis. On the other hand, an inhibitor of caspase-3(-like) proteases did not affect the inhibitory effect of inostamycin on cyclin D1 expression, suggesting that caspase-3(-like) proteases were not responsible for inostamycin-induced G1 arrest.",
keywords = "Caspase-3, Cyclin D1, Inostomycin, p27(KIP1)",
author = "Masaya Imoto and Keiko Tanabe and Siro Simizu and Etsu Tashiro and Minoru Takada and Kazuo Umezawa",
year = "1998",
month = "3",
language = "English",
volume = "89",
pages = "315--322",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Inhibition of cyclin D1 expression and induction of apoptosis by inostamycin in small cell lung carcinoma cells

AU - Imoto, Masaya

AU - Tanabe, Keiko

AU - Simizu, Siro

AU - Tashiro, Etsu

AU - Takada, Minoru

AU - Umezawa, Kazuo

PY - 1998/3

Y1 - 1998/3

N2 - Previously, we demonstrated that inostamycin, an inhibitor of phosphatidylinositol turnover, caused cell cycle arrest at the G1 phase, inhibiting the expression of cyclins D1 and E in normal cells. In the present study, we examined the effects of inostamycin on cell cycle progression and apoptosis in human small cell lung carcinoma Ms-1 cells. Treatment of exponentially proliferating Ms-1 cells with low concentrations of inostamycin caused cells to accumulate in the G1 phase. We found that inostamycin decreased cyclin D, and increased cyclin-dependent kinase inhibitors such as p21(WAF1) and p27(KIP1) in Ms-1 cells. On the other hand, higher concentrations of inostamycin induced morphological apoptosis and DNA fragmentation in Ms-1 cells without affecting the expression of p53, Bcl-2 and Bax. Inostamycin-induced apoptosis was suppressed by an inhibitor of caspase-3, and a 17 kDa fragment of activated caspase-3 was detected following inostamycin treatment. Therefore, caspase-3(-like) would appear to be involved in inostamycin-induced apoptosis. On the other hand, an inhibitor of caspase-3(-like) proteases did not affect the inhibitory effect of inostamycin on cyclin D1 expression, suggesting that caspase-3(-like) proteases were not responsible for inostamycin-induced G1 arrest.

AB - Previously, we demonstrated that inostamycin, an inhibitor of phosphatidylinositol turnover, caused cell cycle arrest at the G1 phase, inhibiting the expression of cyclins D1 and E in normal cells. In the present study, we examined the effects of inostamycin on cell cycle progression and apoptosis in human small cell lung carcinoma Ms-1 cells. Treatment of exponentially proliferating Ms-1 cells with low concentrations of inostamycin caused cells to accumulate in the G1 phase. We found that inostamycin decreased cyclin D, and increased cyclin-dependent kinase inhibitors such as p21(WAF1) and p27(KIP1) in Ms-1 cells. On the other hand, higher concentrations of inostamycin induced morphological apoptosis and DNA fragmentation in Ms-1 cells without affecting the expression of p53, Bcl-2 and Bax. Inostamycin-induced apoptosis was suppressed by an inhibitor of caspase-3, and a 17 kDa fragment of activated caspase-3 was detected following inostamycin treatment. Therefore, caspase-3(-like) would appear to be involved in inostamycin-induced apoptosis. On the other hand, an inhibitor of caspase-3(-like) proteases did not affect the inhibitory effect of inostamycin on cyclin D1 expression, suggesting that caspase-3(-like) proteases were not responsible for inostamycin-induced G1 arrest.

KW - Caspase-3

KW - Cyclin D1

KW - Inostomycin

KW - p27(KIP1)

UR - http://www.scopus.com/inward/record.url?scp=15644372283&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15644372283&partnerID=8YFLogxK

M3 - Article

C2 - 9600126

AN - SCOPUS:15644372283

VL - 89

SP - 315

EP - 322

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 3

ER -