Dietary compounds that induce cancer preventive phase 2 enzymes activate apoptosis at comparable doses in HT29 colon carcinoma cells

Ward G. Kirlin, Jiyang Cai, Mary J. DeLong, Emma J. Patten, Dean P. Jones

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Dietary agents that induce glutathione S-transferases and related detoxification systems (Phase 2 enzyme inducers) are thought to prevent cancer by enhancing elimination of chemical carcinogens. The present study shows that compounds of this group (benzyl isothiocyanate, allyl sulfide, dimethyl fumarate, butylated hydroxyanisole) activated apoptosis in human colon carcinoma (HT29) cells in culture over the same concentration ranges that elicited increases in enzyme activity (5-25, 25-100, 10-100, 15-60 μmol/L, respectively). Pretreatment of cells with sodium butyrate, an agent that induces HT29 cell differentiation, resulted in parallel increases in Phase 2 enzyme activities and induction of apoptosis in response to the inducers. Cell death characteristics included apoptotic morphological changes, appearance of cells at sub-G1 phase on flow cytometry, caspase activation, DNA fragmentation and TUNEL-positive staining. The results suggest that dietary Phase 2 inducers may protect against cancer by a mechanism distinct from and in addition to that associated with enhanced elimination of carcinogens. If this occurs in vivo, diets high in such compounds could eliminate precancerous cells by apoptosis at time points well after initial exposure to chemical mutagens and carcinogens.

Original languageEnglish (US)
Pages (from-to)1827-1835
Number of pages9
JournalJournal of Nutrition
Volume129
Issue number10
StatePublished - 1999
Externally publishedYes

Fingerprint

carcinogens
Carcinogens
carcinoma
colon
HT29 Cells
Colon
apoptosis
Apoptosis
Carcinoma
neoplasms
Enzymes
dosage
enzymes
benzyl isothiocyanate
enzyme activity
Butylated Hydroxyanisole
butylated hydroxyanisole
Neoplasms
Enzyme Induction
Butyric Acid

Keywords

  • Apoptosis
  • Butyrate
  • Glutathione S- transferase
  • Human colon carcinoma cells
  • NAD(P)H:quinone reductase

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Cite this

Dietary compounds that induce cancer preventive phase 2 enzymes activate apoptosis at comparable doses in HT29 colon carcinoma cells. / Kirlin, Ward G.; Cai, Jiyang; DeLong, Mary J.; Patten, Emma J.; Jones, Dean P.

In: Journal of Nutrition, Vol. 129, No. 10, 1999, p. 1827-1835.

Research output: Contribution to journalArticle

Kirlin, Ward G. ; Cai, Jiyang ; DeLong, Mary J. ; Patten, Emma J. ; Jones, Dean P. / Dietary compounds that induce cancer preventive phase 2 enzymes activate apoptosis at comparable doses in HT29 colon carcinoma cells. In: Journal of Nutrition. 1999 ; Vol. 129, No. 10. pp. 1827-1835.
@article{04607d8e51484c95b30925a91a279337,
title = "Dietary compounds that induce cancer preventive phase 2 enzymes activate apoptosis at comparable doses in HT29 colon carcinoma cells",
abstract = "Dietary agents that induce glutathione S-transferases and related detoxification systems (Phase 2 enzyme inducers) are thought to prevent cancer by enhancing elimination of chemical carcinogens. The present study shows that compounds of this group (benzyl isothiocyanate, allyl sulfide, dimethyl fumarate, butylated hydroxyanisole) activated apoptosis in human colon carcinoma (HT29) cells in culture over the same concentration ranges that elicited increases in enzyme activity (5-25, 25-100, 10-100, 15-60 μmol/L, respectively). Pretreatment of cells with sodium butyrate, an agent that induces HT29 cell differentiation, resulted in parallel increases in Phase 2 enzyme activities and induction of apoptosis in response to the inducers. Cell death characteristics included apoptotic morphological changes, appearance of cells at sub-G1 phase on flow cytometry, caspase activation, DNA fragmentation and TUNEL-positive staining. The results suggest that dietary Phase 2 inducers may protect against cancer by a mechanism distinct from and in addition to that associated with enhanced elimination of carcinogens. If this occurs in vivo, diets high in such compounds could eliminate precancerous cells by apoptosis at time points well after initial exposure to chemical mutagens and carcinogens.",
keywords = "Apoptosis, Butyrate, Glutathione S- transferase, Human colon carcinoma cells, NAD(P)H:quinone reductase",
author = "Kirlin, {Ward G.} and Jiyang Cai and DeLong, {Mary J.} and Patten, {Emma J.} and Jones, {Dean P.}",
year = "1999",
language = "English (US)",
volume = "129",
pages = "1827--1835",
journal = "Journal of Nutrition",
issn = "0022-3166",
publisher = "American Society for Nutrition",
number = "10",

}

TY - JOUR

T1 - Dietary compounds that induce cancer preventive phase 2 enzymes activate apoptosis at comparable doses in HT29 colon carcinoma cells

AU - Kirlin, Ward G.

AU - Cai, Jiyang

AU - DeLong, Mary J.

AU - Patten, Emma J.

AU - Jones, Dean P.

PY - 1999

Y1 - 1999

N2 - Dietary agents that induce glutathione S-transferases and related detoxification systems (Phase 2 enzyme inducers) are thought to prevent cancer by enhancing elimination of chemical carcinogens. The present study shows that compounds of this group (benzyl isothiocyanate, allyl sulfide, dimethyl fumarate, butylated hydroxyanisole) activated apoptosis in human colon carcinoma (HT29) cells in culture over the same concentration ranges that elicited increases in enzyme activity (5-25, 25-100, 10-100, 15-60 μmol/L, respectively). Pretreatment of cells with sodium butyrate, an agent that induces HT29 cell differentiation, resulted in parallel increases in Phase 2 enzyme activities and induction of apoptosis in response to the inducers. Cell death characteristics included apoptotic morphological changes, appearance of cells at sub-G1 phase on flow cytometry, caspase activation, DNA fragmentation and TUNEL-positive staining. The results suggest that dietary Phase 2 inducers may protect against cancer by a mechanism distinct from and in addition to that associated with enhanced elimination of carcinogens. If this occurs in vivo, diets high in such compounds could eliminate precancerous cells by apoptosis at time points well after initial exposure to chemical mutagens and carcinogens.

AB - Dietary agents that induce glutathione S-transferases and related detoxification systems (Phase 2 enzyme inducers) are thought to prevent cancer by enhancing elimination of chemical carcinogens. The present study shows that compounds of this group (benzyl isothiocyanate, allyl sulfide, dimethyl fumarate, butylated hydroxyanisole) activated apoptosis in human colon carcinoma (HT29) cells in culture over the same concentration ranges that elicited increases in enzyme activity (5-25, 25-100, 10-100, 15-60 μmol/L, respectively). Pretreatment of cells with sodium butyrate, an agent that induces HT29 cell differentiation, resulted in parallel increases in Phase 2 enzyme activities and induction of apoptosis in response to the inducers. Cell death characteristics included apoptotic morphological changes, appearance of cells at sub-G1 phase on flow cytometry, caspase activation, DNA fragmentation and TUNEL-positive staining. The results suggest that dietary Phase 2 inducers may protect against cancer by a mechanism distinct from and in addition to that associated with enhanced elimination of carcinogens. If this occurs in vivo, diets high in such compounds could eliminate precancerous cells by apoptosis at time points well after initial exposure to chemical mutagens and carcinogens.

KW - Apoptosis

KW - Butyrate

KW - Glutathione S- transferase

KW - Human colon carcinoma cells

KW - NAD(P)H:quinone reductase

UR - http://www.scopus.com/inward/record.url?scp=0032882988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032882988&partnerID=8YFLogxK

M3 - Article

VL - 129

SP - 1827

EP - 1835

JO - Journal of Nutrition

JF - Journal of Nutrition

SN - 0022-3166

IS - 10

ER -