Induction of apoptosis in KB cells by pingyangmycin

Pingyangmycin (PYM; Bleomycin A(5)), an antitumour antibiotic is curl-entry used during anticancer therapy. Previous experiments demonstrated that the therapeutic efficiency of PYM for treatment of malignant tumours is consid ered to be related to its ability to cause DNA strand breaks in vitro. Howe ver, very little is known about the interaction of PYM with the target cell s, and it is still unclear how PYM enters the cells. In this study, cell de ath induced by PYM was studied in a human squamous cell carcinoma cell line (KB cells). In order to determine if cell death occurred by necrosis (repr oductive cell death) or apoptosis (programmed cell death), KB cells were ex posed to different concentrations of PYM and evaluated by biochemical and m orphological criteria. Our results indicate that KB cells displayed an arre st in the G(2)-M phase of the cell cycle and became enlarged and polynuclea ted before dying at the low concentrations of PYM. In contrast, when cells were exposed to high concentrations of PYM, morphological changes identical to those usually associated with apoptosis were observed as well as intern ucleosomal digestion of genomic DNA. In conclusion, we demonstrate that PYM is able to induce two distinct modes of cell death depending on the doses of PYM. (C) 2000 Elsevier Science Ltd. All rights reserved.