Tumor-specific cytotoxicity and type of cell death induced by beta-cyclodextrin benzaldehyde inclusion compound.
The cytotoxicity of beta-cyclodextrin benzaldehyde inclusion compound (CDBA) against human normal and cancer cell lines was investigated. CDBA showed slightly higher cytotoxicity against human tumor cell lines, as compared to normal cells, with a tumor-specificity index of 2.2. Human myelogenous leukemia cell lines (HL-60, ML-1, KG-1) were the most sensitive to CDBA, followed by human oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4) and human glioblastoma (T98G, U87MG). Human normal cells (gingival fibroblasts, pulp cells, periodontal ligament fibroblasts) were the most resistant. CDBA induced internucleosomal DNA fragmentation in HL-60 cells and caspase-3, -8, -9 activation, but to a much lesser extent than that attained by UV irradiation or actinomycin D. On the other hand, CDBA did not induce DNA fragmentation, nor caspase activation in HSC-2, HSC-4 or T98G cells. Electron microscopy demonstrated that CDBA induced the destruction of mitochondrial structure and digestion of broken organelles by secondary lysosomes in all of these cells. CDBA also increased the number of acidic organelles as judged by acridine orange staining. The present study suggests that CDBA induces autophagic cell death in cancer cell lines.
Liu
Yu
Y
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China. liuyu4145@sina.com
Sakagami
Hiroshi
H
Hashimoto
Ken
K
Kikuchi
Hirotaka
H
Amano
Osamu
O
Ishihara
Mariko
M
Kanda
Yumiko
Y
Kunii
Shiro
S
Kochi
Mutsuyuki
M
Zhang
Wei
W
Yu
Guangyan
G
D001547:Benzaldehydes / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology; D018922:HL-60 Cells; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology; D009055:Mouth / Q000166:cytology; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy*; D047392:beta-Cyclodextrins / Q000494:pharmacology*
D001547:Benzaldehydes; D047392:beta-Cyclodextrins; C050452:beta-cyclodextrin-benzaldehyde