Beta-lapachone inhibits proliferation and induces apoptosis in retinoblastoma cell lines.
OBJECTIVE
To investigate the cytotoxicity of beta-lapachone, a potent agent that may selectively target tumour cells, in retinoblastoma (RB) cell lines.


METHODS
Growth inhibitory effects of beta-lapachone were evaluated in Y79, WERI-RB1, and RBM human retinoblastoma cell lines. Pro-apoptotic effects of beta-lapachone were evaluated in Y79 cells by detection of caspase 3/7 activity, by enzyme-linked immunosorbent assay for nucleosome fragments, and by cellular morphological analysis.


RESULTS
Beta-lapachone induced significant dose-dependent growth inhibitory effects in all three retinoblastoma cell lines. The 50% growth inhibitory concentration (IC(50)) of this agent was 1.9 microM in Y79 cells, 1.3 microM in WERI-RB1 cells, and 0.9 microM in RBM cells. Beta-lapachone also induced proapoptotic effects in RB cells. Treatment of Y79 cells with 1.9 microM beta-lapachone (IC(50)) resulted in a peak, fourfold induction of caspase 3/7 activity at 72 h post-treatment; a peak, 5.6-fold increase in nucleosome fragments at 96 h post-treatment; and a peak, 1.7-fold increase in the frequency of apoptotic cells at 48 h post-treatment, relative to vehicle-treated controls.


CONCLUSIONS
Beta-lapachone induced potent cytotoxic effects in RB cell lines at low micromolar concentrations, suggesting this agent could be useful in the clinical management of RB.
Shah
H R
HR
Department of Ophthalmology, University of California at San Francisco, San Francisco, CA, USA.
Conway
R M
RM
Van Quill
K R
KR
Madigan
M C
MC
Howard
S A
SA
Qi
J
J
Weinberg
V
V
O'Brien
J M
JM
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053148:Caspase 3 / Q000096:biosynthesis; D053179:Caspase 7 / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D009285:Naphthoquinones / Q000494:pharmacology*; D019572:Retinal Neoplasms / Q000473:pathology*; D012175:Retinoblastoma / Q000473:pathology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D009285:Naphthoquinones; D018894:Reverse Transcriptase Inhibitors; C014638:beta-lapachone; D053148:Caspase 3; D053179:Caspase 7