RRR-alpha-tocopheryl succinate inhibits the proliferation of human prostatic tumor cells with defective cell cycle/differentiation pathways

Nutr Cancer. 1995;24(2):161-9. doi: 10.1080/01635589509514404.

Abstract

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)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Antineoplastic Agents / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Division / drug effects
  • Cell Division / physiology
  • DNA, Neoplasm / biosynthesis
  • DNA, Neoplasm / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Time Factors
  • Tocopherols
  • Transforming Growth Factor beta / pharmacology
  • Tumor Cells, Cultured
  • Vitamin E / analogs & derivatives*
  • Vitamin E / pharmacology

Substances

  • Antineoplastic Agents
  • DNA, Neoplasm
  • Transforming Growth Factor beta
  • Vitamin E
  • Tocopherols