title: Inhibitory effects of different forms of tocopherols, tocopherol phosphates, and tocopherol quinones on growth of colon cancer cells.
abstract: Tocopherols are the major source of dietary vitamin E. In this study, the growth inhibitory effects of different forms of tocopherols (T), tocopheryl phosphates (TP), and tocopherol quinones (TQ) on human colon cancer HCT116 and HT29 cells were investigated. δ-T was more active than γ-T in inhibiting colon cancer cell growth, decreasing cancer cell colony formation, and inducing apoptosis; however, α-T was rather ineffective. Similarly, the rate of cellular uptake also followed the ranking order δ-T > γ-T ≫ α-T. TP and TQ generally had higher inhibitory activities than their parent compounds. Interestingly, the γ forms of TP and TQ were more active than the δ forms in inhibiting cancer cell growth, whereas the α forms were the least effective. The potencies of γ-TQ and δ-TQ (showing IC50 values of ∼0.8 and ∼2 μM on HCT116 cells after a 72 h incubation, respectively) were greater than 100-fold and greater than 20-fold higher, respectively, than those of their parent tocopherols. Induction of cancer cell apoptosis by δ-T, γ-TP, and γ-TQ was characterized by the cleavage of caspase 3 and PARP1 and DNA fragmentation. These studies demonstrated the higher growth inhibitory activity of δ-T than γ-T, the even higher activities of the γ forms of TP and TQ, and the ineffectiveness of the α forms of tocopherol and their metabolites against colon cancer cells.
authors.affiliation: Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854, United States.
authors.forename: Sonia C
authors.initials: SC
authors.lastname: Dolfi
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yang
authors.forename: Mao-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Fei
authors.initials: F
authors.lastname: Guan
authors.forename: Jungil
authors.initials: J
authors.lastname: Hong
authors.forename: Chung S
authors.initials: CS
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D010710:Phosphates / Q000494:pharmacology*; D011809:Quinones / Q000494:pharmacology*; D024505:Tocopherols / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010710:Phosphates; D011809:Quinones; D024505:Tocopherols
references.citation: J Agric Food Chem. 2010 Apr 28;58(8):4844-52
references.pmid: 20222730
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20464-9
references.pmid: 19074288
references.citation: Mol Nutr Food Res. 2010 May;54(5):601-15
references.pmid: 20169582
references.citation: Lipids. 2002 Feb;37(2):173-84
references.pmid: 11908909
references.citation: Carcinogenesis. 2010 Apr;31(4):687-94
references.pmid: 20097733
references.citation: Free Radic Biol Med. 2005 Oct 1;39(7):970-6
references.pmid: 16140216
references.citation: Cancer Prev Res (Phila). 2009 Feb;2(2):143-52
references.pmid: 19155443
references.citation: Nutr Cancer. 2007;59(1):76-81
references.pmid: 17927505
references.citation: Nutr Cancer. 2006;56(1):82-5
references.pmid: 17176221
references.citation: Lipids. 1998 Mar;33(3):295-301
references.pmid: 9560804
references.citation: Biochim Biophys Acta. 2008 Sep;1782(9):498-503
references.pmid: 18555028
references.citation: Clin Exp Pharmacol Physiol. 2010 May;37(5-6):587-92
references.pmid: 20082629
references.citation: Clin Cancer Res. 2009 Jun 15;15(12):4242-9
references.pmid: 19509159
references.citation: J Agric Food Chem. 1999 Apr;47(4):1396-9
references.pmid: 10563987
references.citation: Free Radic Biol Med. 2011 Jun 15;50(12):1794-800
references.pmid: 21443945
references.citation: Front Biosci. 2007 Jan 01;12:2013-9
references.pmid: 17127439
references.citation: Free Radic Biol Med. 2010 Dec 15;49(12):1989-2000
references.pmid: 20923704
references.citation: Int J Cancer. 2010 Feb 15;126(4):852-63
references.pmid: 19626588
references.citation: JAMA. 2009 Jan 7;301(1):52-62
references.pmid: 19066368
references.citation: Cancer Prev Res (Phila). 2012 Apr;5(4):644-54
references.pmid: 22366914
references.citation: Cancer Prev Res (Phila). 2012 May;5(5):701-5
references.pmid: 22490437
references.citation: J Immunol. 2011 Jan 15;186(2):1173-9
references.pmid: 21169551
references.citation: BMC Cancer. 2006 Jan 17;6:13
references.pmid: 16417629
references.citation: Am J Clin Nutr. 2001 Dec;74(6):714-22
references.pmid: 11722951
references.citation: J Agric Food Chem. 2001 Mar;49(3):1508-11
references.pmid: 11312887
references.citation: Carcinogenesis. 2010 Apr;31(4):533-42
references.pmid: 19748925
references.citation: Proc Soc Exp Biol Med. 2000 Sep;224(4):292-301
references.pmid: 10964265
references.citation: JAMA. 2009 Jan 7;301(1):39-51
references.pmid: 19066370
references.citation: Int J Cancer. 2009 Apr 1;124(7):1693-9
references.pmid: 19115203
references.citation: Free Radic Res. 2008 Jul;42(7):674-87
references.pmid: 18654882
references.citation: J Agric Food Chem. 2000 Jun;48(6):2075-81
references.pmid: 10888501
references.citation: Biochem Biophys Res Commun. 2004 May 21;318(1):311-6
references.pmid: 15110789
references.citation: Cancer Prev Res (Phila). 2011 Mar;4(3):404-13
references.pmid: 21372040
references.citation: Mol Nutr Food Res. 2009 Aug;53(8):1030-5
references.pmid: 19557822
references.citation: Carcinogenesis. 2003 Mar;24(3):427-33
references.pmid: 12663501
references.citation: Lipids. 2000 Feb;35(2):171-80
references.pmid: 10757548
references.citation: JAMA. 2011 Oct 12;306(14):1549-56
references.pmid: 21990298