Antiproliferative properties of toremifene on AIDS-related Kaposi's sarcoma cells.
BACKGROUND
Kaposi's sarcoma (KS) is the most common neoplastic apoptosis manifestation of acquired immunodeficiency syndrome. Toremifene is known to upregulate transforming growth factor beta-1 (TGF-beta1), which is a growth-inhibitory factor for KS. We investigated the in vitro effect of toremifene on KS cells.


METHODS
MTT assay was used to measure the growth of four KS cell lines and a human umbilical vein endothelial (HUVE) cell line after incubation with toremifene. Reverse transcription polymerase chain reaction and ELISA were used to measure the level of TGF-beta1.


RESULTS
The IC(50) for the KS cells ranged from 2.2 to 3.2 microM, and 80% of the growth inhibition occurred within 24 h. Toremifene enhanced TGF-beta1 mRNA expression, and the level of TGF-beta1 increased from 103 to 473 pg/ml after 48 h of incubation. Toremifene had no effect on the growth of HUVE cells.


CONCLUSIONS
Toremifene has a specific antiproliferative effect on KS cells. The stimulation of TGF-beta1 production may play a role in the antiproliferative process.
Hong
Angela
A
Department of Radiation Oncology, Sydney Cancer Center, Royal Prince Alfred Hospital, Sydney, Australia. ahong@email.cs.nsw.gov.au
Leigh
Bryan R
BR
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000473:pathology*; D013997:Time Factors; D017312:Toremifene / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D016212:Transforming Growth Factor beta; D017312:Toremifene