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Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on malignant glioma cells.

Komata T, Kanzawa T, Takeuchi H, Germano IM, Schreiber M, Kondo Y, Kondo S - Br. J. Cancer (2003)

Bottom Line: It has not yet been fully determined, however, which CDKI is the best candidate for the treatment of malignant gliomas and whether normal brain tissues are affected by CDKI expression.On the other hand, p27(KIP1) overexpression did not inhibit the viability of cultured astrocytes (RNB) nor induced autophagy.Overall, our findings suggest that gene transfer of p27(KIP1) may be a promising approach for the therapy of malignant gliomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Mount Sinai School of Medicine, New York, NY 10029, USA.

ABSTRACT
Cyclin-dependent kinase inhibitors (CDKIs) are considered as novel anticancer agents because of their ability to induce growth arrest or apoptosis in tumour cells. It has not yet been fully determined, however, which CDKI is the best candidate for the treatment of malignant gliomas and whether normal brain tissues are affected by CDKI expression. Using recombinant adenoviral vectors that express CDKIs (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)), we compared the antitumour effect of CDKIs on malignant glioma cell lines (A172, GB-1, T98G, U87-MG, U251-MG and U373-MG). p27(KIP1) showed higher ability to suppress the growth of all tumour cells tested than other CDKIs. Interestingly, overexpression of p27(KIP1) induced autophagic cell death, but not apoptosis in tumour cells. On the other hand, p27(KIP1) overexpression did not inhibit the viability of cultured astrocytes (RNB) nor induced autophagy. Overall, our findings suggest that gene transfer of p27(KIP1) may be a promising approach for the therapy of malignant gliomas.

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Effect of AdMH4p27 on induction of autophagy. At 72 h after the adenoviral infection with AdBHGΔl,3 or AdMH4p27, U373-MG or RNB cells were treated with 1 μg ml−1 of acridine orange, and incubated at 37°C for 15 min. Viable cells were observed under the fluorescence microscope. Results shown are representative of three independent experiments.
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fig3: Effect of AdMH4p27 on induction of autophagy. At 72 h after the adenoviral infection with AdBHGΔl,3 or AdMH4p27, U373-MG or RNB cells were treated with 1 μg ml−1 of acridine orange, and incubated at 37°C for 15 min. Viable cells were observed under the fluorescence microscope. Results shown are representative of three independent experiments.

Mentions: To determine the type of cell death induced by AdMH4p27KIP1, we first performed the TUNEL staining. The incidence of TUNEL-positive cells in U373-MG cells treated with AdBHGΔ1,3 or AdMH4p27KIP1 for 3 or 5 days was less than 1%. Next, we investigated the changes in the cellular acidic compartments to detect the occurrence of autophagic cell death. Vital staining of U373-MG cells with acridine orange revealed the appearance of acidic vesicular organelles (AVO) 3 days after AdMH4p27KIP1 infection (Figure 3Figure 3


Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on malignant glioma cells.

Komata T, Kanzawa T, Takeuchi H, Germano IM, Schreiber M, Kondo Y, Kondo S - Br. J. Cancer (2003)

Effect of AdMH4p27 on induction of autophagy. At 72 h after the adenoviral infection with AdBHGΔl,3 or AdMH4p27, U373-MG or RNB cells were treated with 1 μg ml−1 of acridine orange, and incubated at 37°C for 15 min. Viable cells were observed under the fluorescence microscope. Results shown are representative of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747579&req=5

fig3: Effect of AdMH4p27 on induction of autophagy. At 72 h after the adenoviral infection with AdBHGΔl,3 or AdMH4p27, U373-MG or RNB cells were treated with 1 μg ml−1 of acridine orange, and incubated at 37°C for 15 min. Viable cells were observed under the fluorescence microscope. Results shown are representative of three independent experiments.
Mentions: To determine the type of cell death induced by AdMH4p27KIP1, we first performed the TUNEL staining. The incidence of TUNEL-positive cells in U373-MG cells treated with AdBHGΔ1,3 or AdMH4p27KIP1 for 3 or 5 days was less than 1%. Next, we investigated the changes in the cellular acidic compartments to detect the occurrence of autophagic cell death. Vital staining of U373-MG cells with acridine orange revealed the appearance of acidic vesicular organelles (AVO) 3 days after AdMH4p27KIP1 infection (Figure 3Figure 3

Bottom Line: It has not yet been fully determined, however, which CDKI is the best candidate for the treatment of malignant gliomas and whether normal brain tissues are affected by CDKI expression.On the other hand, p27(KIP1) overexpression did not inhibit the viability of cultured astrocytes (RNB) nor induced autophagy.Overall, our findings suggest that gene transfer of p27(KIP1) may be a promising approach for the therapy of malignant gliomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Mount Sinai School of Medicine, New York, NY 10029, USA.

ABSTRACT
Cyclin-dependent kinase inhibitors (CDKIs) are considered as novel anticancer agents because of their ability to induce growth arrest or apoptosis in tumour cells. It has not yet been fully determined, however, which CDKI is the best candidate for the treatment of malignant gliomas and whether normal brain tissues are affected by CDKI expression. Using recombinant adenoviral vectors that express CDKIs (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)), we compared the antitumour effect of CDKIs on malignant glioma cell lines (A172, GB-1, T98G, U87-MG, U251-MG and U373-MG). p27(KIP1) showed higher ability to suppress the growth of all tumour cells tested than other CDKIs. Interestingly, overexpression of p27(KIP1) induced autophagic cell death, but not apoptosis in tumour cells. On the other hand, p27(KIP1) overexpression did not inhibit the viability of cultured astrocytes (RNB) nor induced autophagy. Overall, our findings suggest that gene transfer of p27(KIP1) may be a promising approach for the therapy of malignant gliomas.

Show MeSH
Related in: MedlinePlus