Effects of combinations of 7beta-hydroxycholesterol and anticancer drugs or ionizing radiation on the proliferation of cultured tumor cells.
Oxysterols compose a large class of natural substances endowed in a number of cases with marked antiproliferative and cytotoxic activities. The consequences of treatments combining 7beta-hydroxycholesterol (7beta-OHC) or XG-142 (a galactose-linked hydrosoluble derivative of 7beta-OHC) with drugs used in cancer chemotherapy or gamma radiation has been evaluated upon a variety of tumor cell lines: Hep-G2, U937, K562 cells, its adriamycin-resistant variant K562 Adr+ and RDM4. Proliferation was assessed by the Uptiblue assay and the [3H]Thymidine incorporation test. Results indicated that 7beta-OHC increased the sensitivity of tumor cells to adriamycin, VP-16, 5-FU and bleomycin to various degrees. 7beta-OHC was found to reinforce the susceptibility of K562 adriamycin-resistant cells to this drug. In RDM4 cells, an enhanced radiosensitivity by 7beta-OHC was also obtained, whereas XG-142 was less efficient in provoking such an effect.
Hyun
Jin Won
JW
Laboratoire de Chimie Organique des Substances Naturelles, ULP associé au CNRS, Strasbourg, France.
Holl
Vincent
V
Weltin
Denis
D
Dufour
Patrick
P
Luu
Bang
B
Bischoff
Pierre
P
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001761:Bleomycin / Q000008:administration & dosage; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D006888:Hydroxycholesterols / Q000008:administration & dosage / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000528:radiation effects*
D006888:Hydroxycholesterols; D011838:Radiation-Sensitizing Agents; D001761:Bleomycin; C011724:cholest-5-en-3 beta,7 alpha-diol; D004317:Doxorubicin; D005472:Fluorouracil