Chemoprevention by isothiocyanates: Molecular basis of apoptosis induction

Research output: Chapter in Book/Report/Conference proceedingChapter

37 Citations (Scopus)

Abstract

An important and promising group of compounds that have a cancer-chemopreventive property are organosulfur compounds, such as isothiocyanates (ITCs). Various ITCs are effective chemoprotective agents against chemical carcinogenesis in experimental animals. Several epidemiological studies also indicated that the dietary consumption of ITCs or ITC-containing foods inversely correlates with the risk of developing lung, breast, and colon cancers, providing evidence that they have a potential to prevent cancer in humans. Mechanistically, ITCs are capable of inhibiting both the formation and development of a cancer cell through multiple pathways; i.e. the inhibition of carcinogen-activating cytochrome P450 mono-oxygenases, induction of carcinogen-detoxifying phase 2 enzymes, induction of apoptosis, and inhibition of cell cycle progression. We have clarified the molecular mechanisms underlying the relationship between cell cycle regulation and apoptosis induced by benzyl ITC (BITC), a major ITC compound isolated from papaya (Carica papaya) fruit. We identified phosphorylated Bcl-2 as a key molecule linking p38 MAPK-dependent cell cycle regulation with the c-Jun N-terminal kinase activation by BITC. We also established that BITC exerts the cytotoxic effect more preferentially in the proliferating cells than in the quiescent cells. Furthermore, p53 was found to be a potential negative regulator of apoptosis induction by BITC in normal epithelial cells through inhibition of cell cycle progression at the G 0/G1 phase. In contrast, treatment with an excessive concentration of BITC resulted in necrotic cell death in an ATP-dependent manner. This review addresses the biological impact of cell death induction by BITC as well as other ITCs and the involved molecules regulating signal pathways.

Original languageEnglish
Title of host publicationForum of Nutrition
Pages170-181
Number of pages12
Volume61
DOIs
Publication statusPublished - 2009

Publication series

NameForum of Nutrition
Volume61
ISSN (Print)16600347

Fingerprint

Isothiocyanates
Chemoprevention
Apoptosis
Cell Cycle
Carica
Carcinogens
Cell Death
Neoplasms
Oxygenases
Enzyme Induction
JNK Mitogen-Activated Protein Kinases
G1 Phase
p38 Mitogen-Activated Protein Kinases
Colonic Neoplasms
Cytochrome P-450 Enzyme System
Epidemiologic Studies
Signal Transduction
Fruit
Lung Neoplasms
Carcinogenesis

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Nutrition and Dietetics

Cite this

Nakamura, Y. (2009). Chemoprevention by isothiocyanates: Molecular basis of apoptosis induction. In Forum of Nutrition (Vol. 61, pp. 170-181). (Forum of Nutrition; Vol. 61). https://doi.org/10.1159/000212749

Chemoprevention by isothiocyanates : Molecular basis of apoptosis induction. / Nakamura, Yoshimasa.

Forum of Nutrition. Vol. 61 2009. p. 170-181 (Forum of Nutrition; Vol. 61).

Research output: Chapter in Book/Report/Conference proceedingChapter

Nakamura, Y 2009, Chemoprevention by isothiocyanates: Molecular basis of apoptosis induction. in Forum of Nutrition. vol. 61, Forum of Nutrition, vol. 61, pp. 170-181. https://doi.org/10.1159/000212749
Nakamura, Yoshimasa. / Chemoprevention by isothiocyanates : Molecular basis of apoptosis induction. Forum of Nutrition. Vol. 61 2009. pp. 170-181 (Forum of Nutrition).
@inbook{70179951b8894aa3ae984edfe6fbfebe,
title = "Chemoprevention by isothiocyanates: Molecular basis of apoptosis induction",
abstract = "An important and promising group of compounds that have a cancer-chemopreventive property are organosulfur compounds, such as isothiocyanates (ITCs). Various ITCs are effective chemoprotective agents against chemical carcinogenesis in experimental animals. Several epidemiological studies also indicated that the dietary consumption of ITCs or ITC-containing foods inversely correlates with the risk of developing lung, breast, and colon cancers, providing evidence that they have a potential to prevent cancer in humans. Mechanistically, ITCs are capable of inhibiting both the formation and development of a cancer cell through multiple pathways; i.e. the inhibition of carcinogen-activating cytochrome P450 mono-oxygenases, induction of carcinogen-detoxifying phase 2 enzymes, induction of apoptosis, and inhibition of cell cycle progression. We have clarified the molecular mechanisms underlying the relationship between cell cycle regulation and apoptosis induced by benzyl ITC (BITC), a major ITC compound isolated from papaya (Carica papaya) fruit. We identified phosphorylated Bcl-2 as a key molecule linking p38 MAPK-dependent cell cycle regulation with the c-Jun N-terminal kinase activation by BITC. We also established that BITC exerts the cytotoxic effect more preferentially in the proliferating cells than in the quiescent cells. Furthermore, p53 was found to be a potential negative regulator of apoptosis induction by BITC in normal epithelial cells through inhibition of cell cycle progression at the G 0/G1 phase. In contrast, treatment with an excessive concentration of BITC resulted in necrotic cell death in an ATP-dependent manner. This review addresses the biological impact of cell death induction by BITC as well as other ITCs and the involved molecules regulating signal pathways.",
author = "Yoshimasa Nakamura",
year = "2009",
doi = "10.1159/000212749",
language = "English",
isbn = "9783805590976",
volume = "61",
series = "Forum of Nutrition",
pages = "170--181",
booktitle = "Forum of Nutrition",

}

TY - CHAP

T1 - Chemoprevention by isothiocyanates

T2 - Molecular basis of apoptosis induction

AU - Nakamura, Yoshimasa

PY - 2009

Y1 - 2009

N2 - An important and promising group of compounds that have a cancer-chemopreventive property are organosulfur compounds, such as isothiocyanates (ITCs). Various ITCs are effective chemoprotective agents against chemical carcinogenesis in experimental animals. Several epidemiological studies also indicated that the dietary consumption of ITCs or ITC-containing foods inversely correlates with the risk of developing lung, breast, and colon cancers, providing evidence that they have a potential to prevent cancer in humans. Mechanistically, ITCs are capable of inhibiting both the formation and development of a cancer cell through multiple pathways; i.e. the inhibition of carcinogen-activating cytochrome P450 mono-oxygenases, induction of carcinogen-detoxifying phase 2 enzymes, induction of apoptosis, and inhibition of cell cycle progression. We have clarified the molecular mechanisms underlying the relationship between cell cycle regulation and apoptosis induced by benzyl ITC (BITC), a major ITC compound isolated from papaya (Carica papaya) fruit. We identified phosphorylated Bcl-2 as a key molecule linking p38 MAPK-dependent cell cycle regulation with the c-Jun N-terminal kinase activation by BITC. We also established that BITC exerts the cytotoxic effect more preferentially in the proliferating cells than in the quiescent cells. Furthermore, p53 was found to be a potential negative regulator of apoptosis induction by BITC in normal epithelial cells through inhibition of cell cycle progression at the G 0/G1 phase. In contrast, treatment with an excessive concentration of BITC resulted in necrotic cell death in an ATP-dependent manner. This review addresses the biological impact of cell death induction by BITC as well as other ITCs and the involved molecules regulating signal pathways.

AB - An important and promising group of compounds that have a cancer-chemopreventive property are organosulfur compounds, such as isothiocyanates (ITCs). Various ITCs are effective chemoprotective agents against chemical carcinogenesis in experimental animals. Several epidemiological studies also indicated that the dietary consumption of ITCs or ITC-containing foods inversely correlates with the risk of developing lung, breast, and colon cancers, providing evidence that they have a potential to prevent cancer in humans. Mechanistically, ITCs are capable of inhibiting both the formation and development of a cancer cell through multiple pathways; i.e. the inhibition of carcinogen-activating cytochrome P450 mono-oxygenases, induction of carcinogen-detoxifying phase 2 enzymes, induction of apoptosis, and inhibition of cell cycle progression. We have clarified the molecular mechanisms underlying the relationship between cell cycle regulation and apoptosis induced by benzyl ITC (BITC), a major ITC compound isolated from papaya (Carica papaya) fruit. We identified phosphorylated Bcl-2 as a key molecule linking p38 MAPK-dependent cell cycle regulation with the c-Jun N-terminal kinase activation by BITC. We also established that BITC exerts the cytotoxic effect more preferentially in the proliferating cells than in the quiescent cells. Furthermore, p53 was found to be a potential negative regulator of apoptosis induction by BITC in normal epithelial cells through inhibition of cell cycle progression at the G 0/G1 phase. In contrast, treatment with an excessive concentration of BITC resulted in necrotic cell death in an ATP-dependent manner. This review addresses the biological impact of cell death induction by BITC as well as other ITCs and the involved molecules regulating signal pathways.

UR - http://www.scopus.com/inward/record.url?scp=67650218497&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650218497&partnerID=8YFLogxK

U2 - 10.1159/000212749

DO - 10.1159/000212749

M3 - Chapter

C2 - 19367121

AN - SCOPUS:67650218497

SN - 9783805590976

VL - 61

T3 - Forum of Nutrition

SP - 170

EP - 181

BT - Forum of Nutrition

ER -