Abstract
Dihydrodiol dehydrogenase (DDH) is frequently detected in cancer cells, and its overexpression correlates with drug resistance, the downregulation of DNA repair mechanisms, increased frequency of tumor recurrence, cancer cell metastasis and poor prognosis. The silencing of DDH expression using siRNA, on the other hand, reduces drug resistance and cancer cell mobility. These data suggest that DDH may be an oncogene-related protein. However, no specific DDH inhibitor has been identified to date. Thus, in this study, we used DDH as a target enzyme in a live-cell enzyme-linked immunosorbent assay to screen Chinese medicinal herb extracts (CMHEs) with the aim of identifying a DDH inhibitor. Using this method, we found 49 among 796 CMHEs that inhibited DDH expression. We selected three potential extracts, which had the highest activity against DDH, for further fractionation using high-performance liquid chromatography. The active ingredient was identified by immunoblot analysis. The function of the active ingredient was characterized by cell function analysis. Our results revealed that the CMHE-purified compounds targeted DDH, inducing autophagy and reducing DNA repair, which in turn enhanced the cytotoxic effects of the anticancer drugs and irradiation.
| Original language | English |
|---|---|
| Pages (from-to) | 577-584 |
| Number of pages | 8 |
| Journal | International Journal of Molecular Medicine |
| Volume | 32 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Sep 2013 |
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Keywords
- Autophagy
- Dihydrodiol dehydrogenase
- Drug detoxification
- Lipid flow
- Oncogene
ASJC Scopus subject areas
- Genetics
Cite this
Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects. / Chiang, Yung Yen; Wang, Shu Li; Yang, Cheng Lin; Yang, Hui Yu; Yang, Hsiu Ching; Sudhakar, J. N.; Lee, Ching Kuo; Huang, Hsiu Wen; Chen, Chien Min; Chiou, Shiow Her; Chiang, Shu Fen; Fang, Hsin Yuan; Chen, Chih Yi; Shieh, Shwn Huey; Chow, Kuan Chih.
In: International Journal of Molecular Medicine, Vol. 32, No. 3, 09.2013, p. 577-584.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects
AU - Chiang, Yung Yen
AU - Wang, Shu Li
AU - Yang, Cheng Lin
AU - Yang, Hui Yu
AU - Yang, Hsiu Ching
AU - Sudhakar, J. N.
AU - Lee, Ching Kuo
AU - Huang, Hsiu Wen
AU - Chen, Chien Min
AU - Chiou, Shiow Her
AU - Chiang, Shu Fen
AU - Fang, Hsin Yuan
AU - Chen, Chih Yi
AU - Shieh, Shwn Huey
AU - Chow, Kuan Chih
PY - 2013/9
Y1 - 2013/9
N2 - Dihydrodiol dehydrogenase (DDH) is frequently detected in cancer cells, and its overexpression correlates with drug resistance, the downregulation of DNA repair mechanisms, increased frequency of tumor recurrence, cancer cell metastasis and poor prognosis. The silencing of DDH expression using siRNA, on the other hand, reduces drug resistance and cancer cell mobility. These data suggest that DDH may be an oncogene-related protein. However, no specific DDH inhibitor has been identified to date. Thus, in this study, we used DDH as a target enzyme in a live-cell enzyme-linked immunosorbent assay to screen Chinese medicinal herb extracts (CMHEs) with the aim of identifying a DDH inhibitor. Using this method, we found 49 among 796 CMHEs that inhibited DDH expression. We selected three potential extracts, which had the highest activity against DDH, for further fractionation using high-performance liquid chromatography. The active ingredient was identified by immunoblot analysis. The function of the active ingredient was characterized by cell function analysis. Our results revealed that the CMHE-purified compounds targeted DDH, inducing autophagy and reducing DNA repair, which in turn enhanced the cytotoxic effects of the anticancer drugs and irradiation.
AB - Dihydrodiol dehydrogenase (DDH) is frequently detected in cancer cells, and its overexpression correlates with drug resistance, the downregulation of DNA repair mechanisms, increased frequency of tumor recurrence, cancer cell metastasis and poor prognosis. The silencing of DDH expression using siRNA, on the other hand, reduces drug resistance and cancer cell mobility. These data suggest that DDH may be an oncogene-related protein. However, no specific DDH inhibitor has been identified to date. Thus, in this study, we used DDH as a target enzyme in a live-cell enzyme-linked immunosorbent assay to screen Chinese medicinal herb extracts (CMHEs) with the aim of identifying a DDH inhibitor. Using this method, we found 49 among 796 CMHEs that inhibited DDH expression. We selected three potential extracts, which had the highest activity against DDH, for further fractionation using high-performance liquid chromatography. The active ingredient was identified by immunoblot analysis. The function of the active ingredient was characterized by cell function analysis. Our results revealed that the CMHE-purified compounds targeted DDH, inducing autophagy and reducing DNA repair, which in turn enhanced the cytotoxic effects of the anticancer drugs and irradiation.
KW - Autophagy
KW - Dihydrodiol dehydrogenase
KW - Drug detoxification
KW - Lipid flow
KW - Oncogene
UR - http://www.scopus.com/inward/record.url?scp=84880420913&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880420913&partnerID=8YFLogxK
U2 - 10.3892/ijmm.2013.1441
DO - 10.3892/ijmm.2013.1441
M3 - Article
C2 - 23857115
AN - SCOPUS:84880420913
VL - 32
SP - 577
EP - 584
JO - International Journal of Molecular Medicine
JF - International Journal of Molecular Medicine
SN - 1107-3756
IS - 3
ER -