Bifunctional Chemopreventive Effects of Adenocaulon himalaicum Through Induction of Detoxification Enzymes and Apoptosis
- Bifunctional Chemopreventive Effects of Adenocaulon himalaicum Through Induction of Detoxification Enzymes and Apoptosis
- 윤지호; 이샛별; 강경수; 이은하; 이희주; 정상훈; 노주원
- Adenocaulon himalaicum; apoptosis; colon cancer; heme oxygenase; Nrf2; quinone reductase
- Issue Date
- Journal of medicinal food
- VOL 16, NO 8, 701-710
- 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.
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