RRR-alpha-tocopheryl succinate inhibits the proliferation of human prostatic tumor cells with defective cell cycle/differentiation pathways.
The RRR-alpha-tocopheryl succinate derivative of vitamin E, referred to as vitamin E succinate (VES), inhibits the proliferation of three metastatic human prostatic cancer cell lines, LNCaP, PC-3, and DU-145. LNCaP is a lymph node-derived androgen-sensitive prostate cell line; these cells are defective for response to transforming growth factor-beta (TGF-beta) but are normal for cell cycle-related tumor suppressor genes: p53 and retinoblastoma (Rb). PC-3 is a bone marrow-derived androgen-insensitive prostate cell line; these cells are defective for both p53 alleles but normal for both Rb alleles. DU-145 is a brain-derived androgen-insensitive prostate cell line; these cells are defective for both p53 and both Rb alleles. VES at 5, 10, and 20 micrograms/ml inhibited DNA synthesis in the three cell lines in a dose-dependent manner. Purified TGF-beta 1 at 1 ng/ml inhibited DNA synthesis of PC-3 cells within 24-72 hours and DU-145 cells at 72 hours but did not inhibit DNA synthesis of LNCaP cells. Previous studies in our laboratory showed that VES growth-inhibited tumor cells secrete biologically active antiproliferative factor TGF-beta s, suggesting that VES's mechanism of growth inhibition may involve the TGF-beta system of growth control.(ABSTRACT TRUNCATED AT 250 WORDS)
Israel
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Division of Nutritional Sciences, University of Texas at Austin 78712-1097, USA.
Sanders
B G
BG
Kline
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D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D024505:Tocopherols; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D016212:Transforming Growth Factor beta; D014810:Vitamin E; D024505:Tocopherols