Reversal of inflammation-associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by wogonin and chrysin

Hao Wei Wang, Chin Ping Lin, Jen Hwey Chiu, Kuan Chih Chow, Kuang Tai Kuo, Chen Sung Lin, Liang Shun Wang

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Dihydrodiol dehydrogenase (DDH) is a member of the aldo-keto reductases superfamily (AKR1C1-AKR1C4), which plays central roles in the metabolism of steroid hormone, prostaglandin and xenobiotics. We have previously detected overexpression of DDH as an indicator of poor prognosis and chemoresistance in human non-small lung cancer (NSCLC). We also found DDH expression to be closely related to chronic inflammatory conditions. The aim of this study was to investigate the links between inflammation, DDH expression and drug resistance in NSCLC cells. We showed that pro-inflammatory mediators including interleukin-6 (IL-6) could induce AKR1C1/1C2 expression in NSCLC cells and increase cellular resistance to cisplatin and adriamycin. This effect was nullified by Safingol, a protein kinase C inhibitor. Moreover, the expression of AKR1C1/1C2 was inversely correlated to NBS1 and apoptosis-inducing factor (AIF). We also showed that IL-6-induced AKR1C1/1C2 expression and drug resistance were inhibited by wogonin and chrysin, which are major flavonoids in Scutellaria baicalensis, a widely used traditional Chinese and Japanese medicine. In conclusion, this study demonstrated novel links of pro-inflammatory signals, AKR1C1/1C2 expression and drug resistance in NSCLC. The protein kinase C pathway may play an important role in this process. Overexpression of AKR1C1/1C2 may serve as a marker of chemoresistance. Further studies are warranted to evaluate wogonin and chrysin as a potential adjuvant therapy for drug-resistant NSCLC, especially for those with AKR1C1/1C2 overexpression.

Original languageEnglish
Pages (from-to)2019-2027
Number of pages9
JournalInternational Journal of Cancer
Volume120
Issue number9
DOIs
Publication statusPublished - May 1 2007
Externally publishedYes

Fingerprint

Drug Resistance
Non-Small Cell Lung Carcinoma
Inflammation
Protein Kinase C
Interleukin-6
Scutellaria baicalensis
Apoptosis Inducing Factor
Protein C Inhibitor
Chinese Traditional Medicine
Xenobiotics
Adjuvant Chemotherapy
Protein Kinase Inhibitors
Flavonoids
Doxorubicin
Cisplatin
Prostaglandins
Lung Neoplasms
Steroids
Hormones
wogonin

Keywords

  • Aldo-keto reductase (AKR)
  • Carcinoma
  • Cytokines
  • Dihydrodiol dehydrogenase
  • Drug resistance
  • Non-small-cell lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Reversal of inflammation-associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by wogonin and chrysin. / Wang, Hao Wei; Lin, Chin Ping; Chiu, Jen Hwey; Chow, Kuan Chih; Kuo, Kuang Tai; Lin, Chen Sung; Wang, Liang Shun.

In: International Journal of Cancer, Vol. 120, No. 9, 01.05.2007, p. 2019-2027.

Research output: Contribution to journalArticle

Wang, Hao Wei ; Lin, Chin Ping ; Chiu, Jen Hwey ; Chow, Kuan Chih ; Kuo, Kuang Tai ; Lin, Chen Sung ; Wang, Liang Shun. / Reversal of inflammation-associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by wogonin and chrysin. In: International Journal of Cancer. 2007 ; Vol. 120, No. 9. pp. 2019-2027.
@article{91c6b161a8b240a6a6ab7bc236c68d2a,
title = "Reversal of inflammation-associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by wogonin and chrysin",
abstract = "Dihydrodiol dehydrogenase (DDH) is a member of the aldo-keto reductases superfamily (AKR1C1-AKR1C4), which plays central roles in the metabolism of steroid hormone, prostaglandin and xenobiotics. We have previously detected overexpression of DDH as an indicator of poor prognosis and chemoresistance in human non-small lung cancer (NSCLC). We also found DDH expression to be closely related to chronic inflammatory conditions. The aim of this study was to investigate the links between inflammation, DDH expression and drug resistance in NSCLC cells. We showed that pro-inflammatory mediators including interleukin-6 (IL-6) could induce AKR1C1/1C2 expression in NSCLC cells and increase cellular resistance to cisplatin and adriamycin. This effect was nullified by Safingol, a protein kinase C inhibitor. Moreover, the expression of AKR1C1/1C2 was inversely correlated to NBS1 and apoptosis-inducing factor (AIF). We also showed that IL-6-induced AKR1C1/1C2 expression and drug resistance were inhibited by wogonin and chrysin, which are major flavonoids in Scutellaria baicalensis, a widely used traditional Chinese and Japanese medicine. In conclusion, this study demonstrated novel links of pro-inflammatory signals, AKR1C1/1C2 expression and drug resistance in NSCLC. The protein kinase C pathway may play an important role in this process. Overexpression of AKR1C1/1C2 may serve as a marker of chemoresistance. Further studies are warranted to evaluate wogonin and chrysin as a potential adjuvant therapy for drug-resistant NSCLC, especially for those with AKR1C1/1C2 overexpression.",
keywords = "Aldo-keto reductase (AKR), Carcinoma, Cytokines, Dihydrodiol dehydrogenase, Drug resistance, Non-small-cell lung",
author = "Wang, {Hao Wei} and Lin, {Chin Ping} and Chiu, {Jen Hwey} and Chow, {Kuan Chih} and Kuo, {Kuang Tai} and Lin, {Chen Sung} and Wang, {Liang Shun}",
year = "2007",
month = "5",
day = "1",
doi = "10.1002/ijc.22402",
language = "English",
volume = "120",
pages = "2019--2027",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "9",

}

TY - JOUR

T1 - Reversal of inflammation-associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by wogonin and chrysin

AU - Wang, Hao Wei

AU - Lin, Chin Ping

AU - Chiu, Jen Hwey

AU - Chow, Kuan Chih

AU - Kuo, Kuang Tai

AU - Lin, Chen Sung

AU - Wang, Liang Shun

PY - 2007/5/1

Y1 - 2007/5/1

N2 - Dihydrodiol dehydrogenase (DDH) is a member of the aldo-keto reductases superfamily (AKR1C1-AKR1C4), which plays central roles in the metabolism of steroid hormone, prostaglandin and xenobiotics. We have previously detected overexpression of DDH as an indicator of poor prognosis and chemoresistance in human non-small lung cancer (NSCLC). We also found DDH expression to be closely related to chronic inflammatory conditions. The aim of this study was to investigate the links between inflammation, DDH expression and drug resistance in NSCLC cells. We showed that pro-inflammatory mediators including interleukin-6 (IL-6) could induce AKR1C1/1C2 expression in NSCLC cells and increase cellular resistance to cisplatin and adriamycin. This effect was nullified by Safingol, a protein kinase C inhibitor. Moreover, the expression of AKR1C1/1C2 was inversely correlated to NBS1 and apoptosis-inducing factor (AIF). We also showed that IL-6-induced AKR1C1/1C2 expression and drug resistance were inhibited by wogonin and chrysin, which are major flavonoids in Scutellaria baicalensis, a widely used traditional Chinese and Japanese medicine. In conclusion, this study demonstrated novel links of pro-inflammatory signals, AKR1C1/1C2 expression and drug resistance in NSCLC. The protein kinase C pathway may play an important role in this process. Overexpression of AKR1C1/1C2 may serve as a marker of chemoresistance. Further studies are warranted to evaluate wogonin and chrysin as a potential adjuvant therapy for drug-resistant NSCLC, especially for those with AKR1C1/1C2 overexpression.

AB - Dihydrodiol dehydrogenase (DDH) is a member of the aldo-keto reductases superfamily (AKR1C1-AKR1C4), which plays central roles in the metabolism of steroid hormone, prostaglandin and xenobiotics. We have previously detected overexpression of DDH as an indicator of poor prognosis and chemoresistance in human non-small lung cancer (NSCLC). We also found DDH expression to be closely related to chronic inflammatory conditions. The aim of this study was to investigate the links between inflammation, DDH expression and drug resistance in NSCLC cells. We showed that pro-inflammatory mediators including interleukin-6 (IL-6) could induce AKR1C1/1C2 expression in NSCLC cells and increase cellular resistance to cisplatin and adriamycin. This effect was nullified by Safingol, a protein kinase C inhibitor. Moreover, the expression of AKR1C1/1C2 was inversely correlated to NBS1 and apoptosis-inducing factor (AIF). We also showed that IL-6-induced AKR1C1/1C2 expression and drug resistance were inhibited by wogonin and chrysin, which are major flavonoids in Scutellaria baicalensis, a widely used traditional Chinese and Japanese medicine. In conclusion, this study demonstrated novel links of pro-inflammatory signals, AKR1C1/1C2 expression and drug resistance in NSCLC. The protein kinase C pathway may play an important role in this process. Overexpression of AKR1C1/1C2 may serve as a marker of chemoresistance. Further studies are warranted to evaluate wogonin and chrysin as a potential adjuvant therapy for drug-resistant NSCLC, especially for those with AKR1C1/1C2 overexpression.

KW - Aldo-keto reductase (AKR)

KW - Carcinoma

KW - Cytokines

KW - Dihydrodiol dehydrogenase

KW - Drug resistance

KW - Non-small-cell lung

UR - http://www.scopus.com/inward/record.url?scp=33947256988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947256988&partnerID=8YFLogxK

U2 - 10.1002/ijc.22402

DO - 10.1002/ijc.22402

M3 - Article

VL - 120

SP - 2019

EP - 2027

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 9

ER -