The chemopreventive effects of Carpesium abrotanoides are mediated by induction of phase II detoxification enzymes and apoptosis in human colorectal cancer cells.
Cancer chemoprevention is thought to occur either by blocking the initiation of or suppressing the promotion of carcinogenesis. Phase II detoxification enzymes are known to play important roles in cancer chemoprevention because they enhance cytoprotection through detoxification and elimination of activated carcinogens at tumor initiation. Apoptosis is one of the most important inhibitory targets for tumor promotion. In this study, we have investigated the cancer chemopreventive activity of the ethanolic extract of Carpesium abrotanoides (CAE). We found that CAE induced quinone reductase [also known as NAD(P)H:quinone oxidoreductase (NQO1)] activity, increased NQO1 mRNA and protein expression, and had a relatively high chemoprevention index (12.04). CAE also significantly activated the antioxidant response element through the nuclear accumulation of NF-E2-related factor 2 in HCT116. Interestingly, we also found that CAE induced apoptosis, as evidenced by the externalization of phosphatidylserine, increased sub-G(0)/G(1) content, chromatin condensation, poly(ADP-ribose) polymerase cleavage, and p53. These data suggest that the chemopreventive effects of C. abrotanoides can result from both the induction of phase II detoxification enzymes and from apoptosis. Thus, CAE could potentially be developed as a cancer chemopreventive agent for prevention or treatment of human cancers.
Natural Products Research Center, Korea Institute of Science and Technology, Gangneung Institute , Gangneung, Gangwon-do, Republic of Korea.
Saet Byoul
SB
Lee
Kyungsu
K
Kang
Hee Ju
HJ
Lee
Ji Ho
JH
Yun
Eun Hye
EH
Jho
Chul Young
CY
Kim
Chu Won
CW
Nho
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D019659:Asteraceae; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D050217:Metabolic Detoxication, Phase II; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012694:Serine / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; D012333:RNA, Messenger; D012694:Serine; D016660:NAD(P)H Dehydrogenase (Quinone); D011065:Poly(ADP-ribose) Polymerases