Antitumour effect of cyclin-dependent kinase inhibitors (p16INK4A, p18INK4C, p19INK4D, p21WAF1/CIP1 and p27KIP1) on malignant glioma cells

• Published in: British journal of cancer 2003-04, Vol.88 (8), p.1277-1280
• Main Authors: Komata, T, Kanzawa, T, Takeuchi, H, Germano, I M, Schreiber, M, Kondo, Y, Kondo, S
• Format: Article
• Language: English
• Subjects: Apoptosis; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell cycle; Cyclin-dependent kinases; Drug Resistance; Epidemiology; Experimental Therapeutics; Kinases; Medical research; Medical sciences; Molecular Medicine; Neurology; Neurosurgery; Oncology; Tumors of the nervous system. Phacomatoses
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6600862

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.