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Titolo:
UCN-01 (7-hydoxystaurosporine) inhibits in vivo growth of human cancer cells through selective perturbation of G1 phase checkpoint machinery
Autore:
Abe, S; Kubota, T; Otani, Y; Furukawa, T; Watanabe, M; Kumai, K; Akiyama, T; Akinaga, S; Kitajima, M;
Indirizzi:
Keio Univ, Sch Med, Dept Surg, Shinjuku Ku, Tokyo 1608582, Japan Keio Univ Tokyo Japan 1608582 pt Surg, Shinjuku Ku, Tokyo 1608582, Japan Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Inst, Nagaizumi, Shizuoka 4118731, Japan Kyowa Hakko Kogyo Co Ltd Nagaizumi Shizuoka Japan 4118731 4118731, Japan
Titolo Testata:
JAPANESE JOURNAL OF CANCER RESEARCH
fascicolo: 5, volume: 92, anno: 2001,
pagine: 537 - 545
SICI:
0910-5050(200105)92:5<537:U(IIVG>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; CYCLIN-DEPENDENT KINASES; HUMAN EPIDERMOID CARCINOMA; PANCREATIC-CANCER; POTENT INHIBITOR; P53 MUTATIONS; G(1) ARREST; NUDE-MICE; APOPTOSIS; 7-HYDROXYSTAUROSPORINE;
Keywords:
UCN-01; human xenografts; in vivo sensitivity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Kubota, T Keio Univ, Sch Med, Dept Surg, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan Keio Univ 35 Shinanomachi Tokyo Japan 1608582 yo 1608582, Japan
Citazione:
S. Abe et al., "UCN-01 (7-hydoxystaurosporine) inhibits in vivo growth of human cancer cells through selective perturbation of G1 phase checkpoint machinery", JPN J CANC, 92(5), 2001, pp. 537-545

Abstract

Mechanisms underlying tumor sensitivity to the antitumor agent UCN-01 (7-hydroxystaurosporine) were examined in the nude mouse model using three human tumor xenografts, two pancreatic cancers (PAN-3-JCK and CRI, 1420) and a breast cancer (MX-1). UCN-01 antitumor activity was evaluated in terms of relative tumor weights in treated and untreated mice bearing the tumor xenografts, The activity of cyclin-dependent kinase 2 (CDK2), levels of p21 and p27 proteins, pRb status and cell cycle were evaluated. Induction of p21 and apoptosis were also assessed immunohistochemically in CRI, 1420. UCN-01 was administered intraperitoneally at a dose of either 5 or 10 mg/kg daily for 5 days followed by a further 5 injections after an interval of 2 days. UCN-01 significantly suppressed the growth of both pancreatic cancers, but was ineffective against MX-I. p21 protein espression was markedly induced inthe UCN-01-sensitive pancreatic carcinoma xenografts at both doses, but p21 induction was only evident in the UCN-01-resistant MX-1 at 10 mg/kg, MX-1exhibited CDK2 activity that was ii-fold higher than that of pancreatic cancer strains, which may explain the resistance of MX-1 to UCN-01 despite the induction of p21 at the dose of 10 mg/kg. The UCN-01-sensitive tumors exhibited G1 arrest and increased levels of apoptosis, changes not observed inresistant MX-1. In conclusion, it appears that a determining factor of in vivo UCN-01 sensitivity involves the balance of CDK2 kinase activity and p21 protein induction, resulting in augmented pRb phosphorylation, G1 cell cycle arrest and apoptosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/10/20 alle ore 23:57:42