Bifunctional chemopreventive effects of Adenocaulon himalaicum through induction of detoxification enzymes and apoptosis.

Abstract

Phase II detoxification enzymes are known to play essential roles in the detoxification and elimination of activated carcinogens during tumor initiation, while apoptosis is one of the most important chemopreventive targets for inhibiting tumor promotion in cancer. In this study, we investigated the cancer chemopreventive activity of two plant extracts, the ethanolic extract of Adenocaulon himalaicum (AHE) and the butanolic fraction of AHE (AHB). Both, the AHE and AHB induced NQO1 activity and had relatively high chemoprevention indices (CI=12.4). The AHE and AHB were associated with increased NQO1 and HO-1 mRNA levels via Nrf2-ARE pathway activation. In addition, the AHB increased CYP1A1 activity through AhR-XRE pathway activation. We also found that the AHE and AHB induced apoptosis, as evidenced by phosphatidylserine externalization, an increase in the sub-G0/G1 content, chromatin condensation, poly(ADP-ribose) polymerase cleavage, and p53 induction. These data suggest that AHE and AHB act as bifunctional inducers and that their chemopreventive effects result from the biphasic induction of phase II detoxification enzymes and apoptosis. Therefore, these results suggest that A. himalaicum plant extracts have potential for use as chemopreventive agents for the prevention and/or treatment of human cancers.

• Authors: Ji Ho Yun, Saet Byoul Lee, Kyungsu Kang, Eun Ha Lee, Hee Ju Lee, Sang Hoon Jung, Chu Won Nho
• Journal: Journal of medicinal food (J Med Food) Vol. 16 Issue 8 Pg. 701-10 (Aug 2013) ISSN: 1557-7600 [Electronic] United States
• PMID: 23957354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-E2-Related Factor 2
• Plant Extracts
• NAD(P)H Dehydrogenase (Quinone)

Topics

• Apoptosis (drug effects)
• Asteraceae (chemistry)
• Cell Line, Tumor
• Chemoprevention
• Humans
• Metabolic Detoxication, Phase II
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Neoplasms (enzymology, metabolism, physiopathology, prevention & control)
• Plant Extracts (chemistry, pharmacology)