Measurement of tamoxifen-induced apoptosis in glioblastoma by cytometric bead analysis of active caspase-3.
Pre-clinical trials of novel drugs for the treatment of glioblastoma often use apoptosis as a measure of anti-tumor effect. Presently, there is no single reliable method to determine whether a cell is apoptotic in glioblastoma. The currently used methods for detecting apoptosis, including terminal deoxynucleotidyl transferase nick-end-labeling, nuclear morphology, DNA laddering, Annexin-V binding, and Western blotting, are subjective, difficult to perform or difficult to quantify in glioblastoma. Cytomeric bead array analysis for active caspase-3 is a recently developed technique, which may allow rapid quantitation of apoptosis in glioblastoma. Tamoxifen (TAM), a drug used in treating breast cancer and more recently for brain tumors, was used to induce apoptosis in human glioblastoma cell lines. This study showed that TAM induced apoptosis via caspase-3 activation. The results also revealed a time- and dose-dependent response of TAM induced caspase-3 activity in glioblastoma. Cytometric bead array provides a rapid technique for measuring apoptosis and the kinetics of caspase-3 activity in glioblastoma.
Zartman
Joy K
JK
University of Colorado Health Sciences Center, The Children's Hospital, Denver, CO 80262, USA.
Foreman
Nicholas K
NK
Donson
Andrew M
AM
Fleitz
Julie M
JM
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry / Q000379:methods*; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases