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Deglycosylated bleomycin triggers apoptosis in laryngeal carcinoma cells in a caspase and reactive oxygen species independent manner
Author(s) -
Brahim Souhir,
Bettaieb Ali,
Kenani Abderraouf
Publication year - 2008
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.2007.00621.x
Subject(s) - bleomycin , apoptosis , reactive oxygen species , programmed cell death , dna fragmentation , clonogenic assay , biology , viability assay , cytotoxicity , cancer research , microbiology and biotechnology , chemistry , biochemistry , in vitro , chemotherapy , genetics
Background: Bleomycin‐A2, a member of a family of glycopeptide antibiotics, has potent antitumor activity against a range of lymphomas, head and neck cancer and germ cell tumors. However, little is known about the biologic activity of the carbohydrate moiety in Bleomycin‐A2‐induced cytotoxicity. Methods: We compared the capacity of Bleomycin‐A2 and its deglycosylated form (deglycoBleomycin‐A2) to induce cell death. Apoptosis was analyzed by cell nuclear staining with Hoechst 33342 dye and DNA fragmentation. The signal transduction pathway was measured through Western blotting and production of reactive oxygen species (ROS). Results: When tested on HEp‐2 laryngeal carcinoma cells, Bleomycin‐A2, and deglycoBleomycin‐A2 decreased cell viability and clonogenic survival, but Bleomycin‐A2 was more toxic than its deglycosylated form. The cell death occurred by apoptosis as identified by condensed chromatin and the formation of apoptotic bodies. While Bleomycin‐A2‐induced apoptosis was dependent on caspase activation and ROS production, deglycoBleomycin‐A2‐triggered apoptosis did not require caspase activation and ROS production. Conclusions: The deglycosylation of Bleomycin‐A2 suppresses the ability of the drug to induce ROS formation without hampering its toxic effect. These observations indicate that deglycoBleomycin‐A2 may demonstrate a less toxic profile than BLM in the clinic.