1. Camptothecin induces urokinase-type plasminogen activator gene-expression in human RC-K8 malignant lymphoma and H69 small cell lung cancer cells
- Author
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Shibakura, Misako, Niiya, Kenji, Kiguchi, Toru, Nakata, Yasunari, and Tanimoto, Mitsune
- Subjects
Lung Neoplasms ,Lymphoma ,H69 ,Antineoplastic Agents, Phytogenic ,Urokinase-Type Plasminogen Activator ,Gene Expression Regulation, Enzymologic ,respiratory tract diseases ,RC-K8 ,Gene Expression Regulation, Neoplastic ,SN38 ,Tumor Cells, Cultured ,uPA ,Humans ,heterocyclic compounds ,Camptothecin ,CPT ,RNA, Messenger ,Carcinoma, Small Cell ,neoplasms - Abstract
We previously reported that anthracyclines, which could generate reactive oxygen species (ROS), could induce the urokinase-type plasminogen activator (uPA) gene expression in human RC-K8 malignant lymphoma cells and in H69 small cell lung cancer (SCLC) cells. In screening other uPA-inducible anti-cancer agents, we found that camptothecin (CPT) and its derivative, SN38, could induce uPA in RC-K8 and H69 cells. CPT and SN38, which are also used for the treatment of lymphoma and SCLC, significantly increased the uPA accumulation in the conditioned media of both cells in a dose-dependent manner. The maximum induction of uPA mRNA levels was observed 24 h after stimulation. Pretreatment with pyrrolidine dithiocarbamate (PDTC), an anti-oxidant, inhibited the CPT-induced uPA mRNA expression. Thus, CPT induces uPA through gene expression, and, therefore, CPT may influence the tumor-cell biology by up-regulating the uPA/plasmin system.
- Published
- 2003