9-Nitrocamptothecin inhibits HIV-1 replication in human peripheral blood lymphocytes: a potential alternative for HIV-infection/AIDS therapy.
The ability of the anti-cancer drug, 9-Nitrocamptothecin (9NC), to inhibit replication of HIV-1 in clinically relevant primary lymphocytic cells was studied. Primary peripheral blood lymphocytes (PBLs) from a non-infected donor were freshly infected with HIV-1 and treated with 9NC by using three different treatment schedules. Cells were monitored for cytotoxicity by the XTT metabolic cell proliferation assay and a sensitive flow cytometric assay that was capable of measuring cell cycle changes and apoptosis. 9NC inhibited replication of HIV-1 in PBLs by greater than 95% in a dose-dependent manner as measured by the level of extracellular HIV-1 p24 release. Similar results were observed, whether 9NC was applied in a single, double, or triple dose regimen. Minimal cytotoxicity was observed for both non-infected and infected PBLs, as determined by the XTT assay. Moreover, 9NC induced apoptosis within 24 hours of drug treatment in freshly infected, but not non-infected, PBLs. The data showed that 9NC reduced replication of HIV-1 in primary human lymphocytes; thus, it indicates the potential clinical utility of this drug as an alternative or adjunct therapy for HIV-infection/AIDS.
Hung
C L
CL
Advanced Bioscience Laboratories, Inc., Kensington, Maryland, USA.
Doniger
J
J
Palini
A
A
Snyder
S W
SW
Radonovich
M F
MF
Brady
J N
JN
Pantazis
P
P
Sadaie
M R
MR
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000821:virology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; C079905:rubitecan; D002166:Camptothecin