Abstract
In this study, we show that the novel synthetic curcumin analog, EF24, induces cell cycle arrest and apoptosis by means of a redox-dependent mechanism in MDA-MB-231 human breast cancer cells and DU-145 human prostate cancer cells. Cell cycle analysis demonstrated that EF24 causes a G2/M arrest in both cell lines, and that this cell cycle arrest is followed by the induction of apoptosis as evidenced by caspase-3 activation, phosphatidylserine externalization and an increased number of cells with a sub-G1 DNA fraction. In addition, we demonstrate that EF24 induces a depolarization of the mitochondrial membrane potential, suggesting that the compound may also induce apoptosis by altering mitochondrial function. EF24, like curcumin, serves as a Michael acceptor reacting with glutathione (GSH) and thioredoxin 1. Reaction of EF24 with these agents in vivo significantly reduced intracellular GSH as well as oxidized GSH in both the wild-type and Bcl-XL overexpressing HT29 human colon cancer cells. We therefore propose that the anticancer effect of a novel curcumin analog, EF24, is mediated in part by redox-mediated induction of apoptosis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 263-275 |
| Number of pages | 13 |
| Journal | Anti-Cancer Drugs |
| Volume | 16 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2005 |
| Externally published | Yes |
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Keywords
- Apoptosis
- Caspase
- DNA fragmentation
- EF24
- G/M cell cycle arrest
- Glutathione
- Mitochondrial membrane depolarization
- Oxidized glutathione
- Phosphatidylserine externalization
- Reactive oxygen species
- Reduction-oxidation (redox)
ASJC Scopus subject areas
- Pharmacology
- Cancer Research
- Oncology
Cite this
EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism. / Adams, Brian K.; Cai, Jiyang; Armstrong, Jeff; Herold, Marike; Lu, Yang J.; Sun, Aiming; Snyder, James P.; Liotta, Dennis C.; Jones, Dean P.; Shoji, Mamoru.
In: Anti-Cancer Drugs, Vol. 16, No. 3, 03.2005, p. 263-275.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism
AU - Adams, Brian K.
AU - Cai, Jiyang
AU - Armstrong, Jeff
AU - Herold, Marike
AU - Lu, Yang J.
AU - Sun, Aiming
AU - Snyder, James P.
AU - Liotta, Dennis C.
AU - Jones, Dean P.
AU - Shoji, Mamoru
PY - 2005/3
Y1 - 2005/3
N2 - In this study, we show that the novel synthetic curcumin analog, EF24, induces cell cycle arrest and apoptosis by means of a redox-dependent mechanism in MDA-MB-231 human breast cancer cells and DU-145 human prostate cancer cells. Cell cycle analysis demonstrated that EF24 causes a G2/M arrest in both cell lines, and that this cell cycle arrest is followed by the induction of apoptosis as evidenced by caspase-3 activation, phosphatidylserine externalization and an increased number of cells with a sub-G1 DNA fraction. In addition, we demonstrate that EF24 induces a depolarization of the mitochondrial membrane potential, suggesting that the compound may also induce apoptosis by altering mitochondrial function. EF24, like curcumin, serves as a Michael acceptor reacting with glutathione (GSH) and thioredoxin 1. Reaction of EF24 with these agents in vivo significantly reduced intracellular GSH as well as oxidized GSH in both the wild-type and Bcl-XL overexpressing HT29 human colon cancer cells. We therefore propose that the anticancer effect of a novel curcumin analog, EF24, is mediated in part by redox-mediated induction of apoptosis.
AB - In this study, we show that the novel synthetic curcumin analog, EF24, induces cell cycle arrest and apoptosis by means of a redox-dependent mechanism in MDA-MB-231 human breast cancer cells and DU-145 human prostate cancer cells. Cell cycle analysis demonstrated that EF24 causes a G2/M arrest in both cell lines, and that this cell cycle arrest is followed by the induction of apoptosis as evidenced by caspase-3 activation, phosphatidylserine externalization and an increased number of cells with a sub-G1 DNA fraction. In addition, we demonstrate that EF24 induces a depolarization of the mitochondrial membrane potential, suggesting that the compound may also induce apoptosis by altering mitochondrial function. EF24, like curcumin, serves as a Michael acceptor reacting with glutathione (GSH) and thioredoxin 1. Reaction of EF24 with these agents in vivo significantly reduced intracellular GSH as well as oxidized GSH in both the wild-type and Bcl-XL overexpressing HT29 human colon cancer cells. We therefore propose that the anticancer effect of a novel curcumin analog, EF24, is mediated in part by redox-mediated induction of apoptosis.
KW - Apoptosis
KW - Caspase
KW - DNA fragmentation
KW - EF24
KW - G/M cell cycle arrest
KW - Glutathione
KW - Mitochondrial membrane depolarization
KW - Oxidized glutathione
KW - Phosphatidylserine externalization
KW - Reactive oxygen species
KW - Reduction-oxidation (redox)
UR - http://www.scopus.com/inward/record.url?scp=20044389847&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20044389847&partnerID=8YFLogxK
U2 - 10.1097/00001813-200503000-00005
DO - 10.1097/00001813-200503000-00005
M3 - Article
C2 - 15711178
AN - SCOPUS:20044389847
VL - 16
SP - 263
EP - 275
JO - Anti-Cancer Drugs
JF - Anti-Cancer Drugs
SN - 0959-4973
IS - 3
ER -