title: Sensitivity of drug-resistant B-cell lines from AIDS-related non-hodgkins-lymphoma to newly synthesized podophyllotoxin derivatives and aza-alkyllysophospholipids - enhanced sensitization by pretreatment with interferon-gamma.
abstract: Non-Hodgkin's lymphoma B cells (NHL-B) often become refractory to conventional chemotherapeutic drugs. The present study investigated the sensitivity of three AIDS-derived NHL-B cell lines to newly synthesized azaalkyllysophospholipids (AALP) and podophyllotoxin derivatives. All three cell lines were sensitive to 5 AALP derivatives and toxicity was detectable at 24 h of culture and was increased at 48 and 72 h of incubation. Toxicity was concentration-dependent and die extent of cytotoxicity varied slightly from one cell line to another. These cell lines were less sensitive to the podophyllotoxin derivatives VP-16, BDPTN and BEPT than to die AALP. This was shown by the extent of cytotoxicity calculated on a molar basis and by the delayed kinetics of lysis. Pretreatment of the tumor cells with IFN-gamma stimulated cell proliferation. IFN-gamma treated tumor cells were also tested for their sensitivity to the various cytotoxic agents. In all cases, the sensitivity of the IFN-gamma pretreated cell lines to the podophyllotoxin derivatives and AALP was significantly enhanced. These findings demonstrate that drug resistant NHL-B cells are sensitive to a new family of AALP and podophyllotoxin derivatives. Further, the sensitivity of the tumor cells was enhanced by treatment with IFN-gamma. The potential clinical use of these new cytotoxic agents to overcome resistance of AIDS-related cell lymphomas is discussed.
authors.affiliation: UNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, 10833 LE CONTE AVE, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, JONSSON COMPREHENS CANC CTR, LOS ANGELES, CA 90024 USA. INST HENRI BEAUFOUR, F-92350 LE PLESSIS ROBINSON, FRANCE. HUNTINGTON MEM HOSP, INST MOLEC MED & TECHNOL, PASADENA, CA 91105 USA. UNIV SO CALIF, SCH MED, DEPT MED, LOS ANGELES, CA 90033 USA.
authors.forename: A
authors.initials: A
authors.lastname: Demidem
authors.forename: C
authors.initials: C
authors.lastname: Broquet
authors.forename: J
authors.initials: J
authors.lastname: Menciahuerta
authors.forename: S
authors.initials: S
authors.lastname: Salahuddin
authors.forename: T
authors.initials: T
authors.lastname: Lam
authors.forename: R
authors.initials: R
authors.lastname: Khan
authors.forename: P
authors.initials: P
authors.lastname: Braquet
authors.forename: A
authors.initials: A
authors.lastname: Levine
authors.forename: B
authors.initials: B
authors.lastname: Bonavida