The proteasome inhibitor bortezomib (Velcade) sensitizes some human tumor cells to Apo2L/TRAIL-mediated apoptosis.
On testing a panel of different human cancer cell lines, we observed that the proteasome inhibitor bortezomib could dramatically sensitize some lines to the apoptotic effects of Apo2L/TRAIL. Certain renal, colon, or breast tumor cell lines were dramatically sensitized, whereas other tumor lines from the same tissue of origin remained resistant. This sensitization did not correlate with either the p53 status of the individual tumor cell lines or their intrinsic sensitivity to Apo2L/TRAIL. Colon cancer cell lines lacking p53 or Bax were sensitized by bortezomib, suggesting that neither p53 nor Bax levels were crucial for sensitization. Although the molecular basis of bortezomib sensitization of tumor cells to Apo2L/TRAIL remains to be determined, this combination can have an enhanced apoptotic effect over either agent alone for certain human cancer cells.
Brooks
Alan D
AD
Basic Research Program, SAIC-Frederick Inc., MD 21702-1201, USA.
Ramirez
Teresa
T
Toh
Uhi
U
Onksen
Jennifer
J
Elliott
Peter J
PJ
Murphy
William J
WJ
Sayers
Thomas J
TJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001897:Boronic Acids; D008024:Ligands; D008562:Membrane Glycoproteins; D061988:Proteasome Inhibitors; D011719:Pyrazines; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D000069286:Bortezomib