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 language | English |
|---|---|
| Pages (from-to) | 315-322 |
| Number of pages | 8 |
| Journal | Japanese Journal of Cancer Research |
| Volume | 89 |
| Issue number | 3 |
| Publication status | Published - 1998 Mar |
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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 journal › Article
}
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 -