Effect of dolastatin 10 on human non-Hodgkin's lymphoma cell lines.
It is crucial to incorporate new and more potent antineoplastic agents in treating non-Hodgkin's lymphoma since standard chemotherapy fails to cause a significant increase in the survival rate. A potential chemotherapeutic agent is dolastatin 10; hence, the objective of our study is to investigate the effect of the antiproliferative agent dolastatin 10 on different grades of non-Hodgkin's lymphoma cell lines. All cell lines exposed to dolastatin 10 initiated an apoptosis process. Alteration of oncogenes and their product may direct the entry of the cells into apoptosis, among these oncogenes are bcl-2 and c-myc. All cell lines tested expressed c-myc and bcl-2 proteins. However, 24 h after exposing the cell lines to 1 ng/ml dolastatin 10, bcl-2 expression was abolished but there was no significant change in c-myc protein expression. The contradictory roles of c-myc in cell proliferation and death require that other gene(s) products regiment the outcomes of c-myc activity on a cell. A possible candidate for such a modifying gene is bcl-2, whose product prolongs cell survival and blocks apoptosis. Given the above, dolastatin 10 induction of cell arrest is the initiating signal to downregulate the antiapoptotic bcl-2 and reactivate the apoptotic pathway. The reductions in bcl-2 may stabilize the c-myc proliferative action and induce apoptosis.
Maki
A
A
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Mohammad
R
R
Raza
S
S
Saleh
M
M
Govindaraju
K D
KD
Pettit
G R
GR
al-Katib
A
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division; D053938:DNA Fragmentation; D047630:Depsipeptides; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D047630:Depsipeptides; D009842:Oligopeptides; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; C064570:dolastatin 10