title: Tocotrienols promote apoptosis in human breast cancer cells by inducing poly(ADP-ribose) polymerase cleavage and inhibiting nuclear factor kappa-B activity.
abstract: OBJECTIVE
  Tocotrienols and tocopherols are members of the vitamin E family, with similar structures; however, only tocotrienols have been reported to achieve potent anti-cancer effects. The study described here has evaluated anti-cancer activity of vitamin E to elucidate mechanisms of cell death, using human breast cancer cells.
  
  
  METHODS
  Anti-cancer activity of a tocotrienol-rich fraction (TRF) and a tocotrienol-enriched fraction (TEF) isolated from palm oil, as well as pure vitamin E analogues (α-tocopherol, α-, δ- and γ-tocotrienols) were studied using highly aggressive triple negative MDA-MB-231 cells and oestrogen-dependent MCF-7 cells, both of human breast cancer cell lines. Cell population growth was evaluated using a Coulter particle counter. Cell death mechanism, poly(ADP-ribose) polymerase cleavage and levels of NF-κB were determined using commercial ELISA kits.
  
  
  RESULTS
  Tocotrienols exerted potent anti-proliferative effects on both types of cell by inducing apoptosis, the underlying mechanism of cell death being ascertained using respective IC50 concentrations of all test compounds. There was marked induction of apoptosis in both cell lines by tocotrienols compared to treatment with Paclitaxel, which was used as positive control. This activity was found to be associated with cleavage of poly(ADP-ribose) polymerase (a DNA repair protein), demonstrating involvement of the apoptotic cell death signalling pathway. Tocotrienols also inhibited expression of nuclear factor kappa-B (NF-κB), which in turn can increase sensitivity of cancer cells to apoptosis.
  
  
  CONCLUSIONS
  Tocotrienols induced anti-proliferative and apoptotic effects in association with DNA fragmentation, poly(ADP-ribose) polymerase cleavage and NF-κB inhibition in the two human breast cancer cell lines.
authors.affiliation: Malaysian Palm Oil Board, Selangor, 43000, Malaysia.
authors.forename: R
authors.initials: R
authors.lastname: Loganathan
authors.forename: K R
authors.initials: KR
authors.lastname: Selvaduray
authors.forename: K
authors.initials: K
authors.lastname: Nesaretnam
authors.forename: A K
authors.initials: AK
authors.lastname: Radhakrishnan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology*; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology*; D053938:DNA Fragmentation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors; D017239:Paclitaxel / Q000494:pharmacology; D000073878:Palm Oil; D010938:Plant Oils / Q000737:chemistry; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D059748:Proteolysis; D011933:Reagent Kits, Diagnostic; D015398:Signal Transduction; D024508:Tocotrienols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002839:Chromans; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D010938:Plant Oils; D011933:Reagent Kits, Diagnostic; D024508:Tocotrienols; D014810:Vitamin E; C082097:tocotrienol, delta; C013649:plastochromanol 8; D000073878:Palm Oil; C082032:tocotrienol, alpha; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D017239:Paclitaxel