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, Ching-Heng; Wang, Liang Shun

doi:10.1002/ijc.22402

Cited by 101 publications

(94 citation statements)

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“…Eletrophoresis was carried out in two 10% polyacrylamide gels with 4.5% stacking. One gel was processed for immunoblotting (20)(21)(22)(23)(24)(25)(26), and the other gel was stained with Coomassie blue. After electrophoresis, proteins on the first gel were transferred to a nitrocellulose membrane for immunoblotting.…”

Section: Methodsmentioning

confidence: 99%

“…Using differential display alone or in combination with microarray, we previously identified a spectrum of NSCLCspecific tumor markers, such as dihydrodiol dehydrogenase (DDH), c-MET, matrix metalloproteinase (MMP) and short oncostatin M receptor (OSMRs), which were closely associated with resistance to chemotherapy, tumor recurrence, metastasis and poor prognosis (20)(21)(22)(23)(24). Although we expected that DDH would correlate with drug resistance (20)(21)(22) and MMP with tumor metastasis (23), DDH was not directly involved in cisplatin deactivation.…”

Section: Introductionmentioning

confidence: 99%

“…Although we expected that DDH would correlate with drug resistance (20)(21)(22) and MMP with tumor metastasis (23), DDH was not directly involved in cisplatin deactivation. However, since DDH overexpression is closely related to tobacco smoking, and tobacco smoking is the key risk factor for carcinogenesis and disease progression of lung cancer, we used the same methods to examine gene expression profiles in biopsy specimens from smokers and nonsmokers, and we detected that hepatocyte growth factor (HGF) was frequently overexpressed in smokers with NSCLC.…”

Section: Introductionmentioning

confidence: 99%

“…Although nicotine per se is not directly associated with tumorigenesis, catalyzed nicotine is carcinogenic (10,11). In addition, nicotine induces NSCLC growth, and increases angiogenesis in tumors probably via activating nicotinic acetylcholine receptor (nAchR), epidermal growth factor receptor (EGFR) and .Using differential display alone or in combination with microarray, we previously identified a spectrum of NSCLCspecific tumor markers, such as dihydrodiol dehydrogenase (DDH), c-MET, matrix metalloproteinase (MMP) and short oncostatin M receptor (OSMRs), which were closely associated with resistance to chemotherapy, tumor recurrence, metastasis and poor prognosis (20)(21)(22)(23)(24) …”

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confidence: 99%

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Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer

et al. 2013

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Abstract. Our previous study showed that patients with advanced stages of non-small cell lung cancer (NSCLC) were frequently detected with upregulation of hepatocyte growth factor (HGF). In vitro, HGF reduced expression of apoptosis-inducing factor (AIF) and cisplatin sensitivity in NSCLC cells. The effect of HGF was via HGF receptor (c-MET) and the downstream effector, focal adhesion kinase (FAK). In this study, we determined the prognostic value of AIF in NSCLC patients. AIF expression was determined by immunohistochemistry and immunoblotting. Our data show that AIF expression was associated with better prognosis. Expression of AIF inversely correlated with that of positive NSCLC markers, e.g., dihydrodiol dehydrogenase (DDH), c-MET, short oncostatin M receptor (OSMRs), matrix metalloproteinase (MMP)-1, and HER2/neu, which were closely associated with drug resistance, tumor recurrence, metastasis and poor prognosis. Noteworthy, silence of HER2/neu gene expression increases AIF level and drug sensitivity. Addition of HGF inhibits AIF expression in HER2/neu-silenced cells. These results suggested that both HGF and HER2/neu affect drug resistance by regulating AIF expression in NSCLC. IntroductionLung cancer is one of the leading causes of cancer death worldwide. In the United States, the annual mortality rate of lung cancer (estimated 180,000 deaths, male: 73.5/10 5 personyear; female: 41.5/10 5 person-year) is approximately 30% of total cancer-related deaths (1), and nearly 85-90% of lung cancer deaths are attributed to tobacco smoking (2). In Taiwan, the annual mortality rate of lung cancer is approximately 20% (estimated 6,000 deaths, male: 21/10 5 person-year; female: 10.3/10 5 person-year) (3). Lung carcinoma is categorized into small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC) with neuroendocrine features of the cancer cells. Based on the histopathological characteristics, NSCLC can be subcategorized into adenocarcinoma (ADC), squamous cell carcinoma and large cell carcinoma (4). Of note, among these, ADC, which is associated with a higher frequency of drug resistance and mortality than the other types, is most commonly found in women and smokers (5).Previous studies have indicated that tobacco smoking is a key risk factor for lung cancer (1,2,5,6). In patients with stage I NSCLC, we demonstrated that tobacco smoking and tumor size, but not visceral pleural invasion, are major factors influencing overall and disease-free survival (6). Moreover, accumulated evidence showed that NSCLC patients who continued to smoke were more resistant to chemotherapy and irradiation, and had poorer prognosis (6-9). Although nicotine per se is not directly associated with tumorigenesis, catalyzed nicotine is carcinogenic (10,11). In addition, nicotine induces NSCLC growth, and increases angiogenesis in tumors probably via activating nicotinic acetylcholine receptor (nAchR), epidermal growth factor receptor (EGFR) and .Using differential display alone or in combination with microarray, we previously identifi...

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer

et al. 2013

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“…The flavonoid has been purified, with a defined chemical structure (Fig. 1), and in addition to the various pharmacological effects that it exerts, baicalein has been widely used to treat various inflammatory diseases, allergies, thrombosis and ischemia, as well as being a scavenger of oxygen free radicals (3)(4)(5)(6)(7)(8)(9)(10). Previously, it has been shown that bacailein not only has a therapeutic effect on non-tumorous diseases, such as acute liver failure and acute myocardial ischemia (11,12), but it also exerts an inhibitory effect on tumor diseases, including colorectal, prostate, liver, lung, skin, stomach and ovarian cancer (13)(14)(15)(16)(17).…”

Section: Chemical Structure and Physiological Function Of Baicaleinmentioning

confidence: 99%

Latest research progress in the correlation between baicalein and breast cancer invasion and metastasis

Yan

Gao

et al. 2016

Molecular and Clinical Oncology

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Abstract. Breast cancer is one of the most commonly occurring female malignant tumors. According to the 2012 GLOBOCAN statistics, produced by the International Agency for Research On Cancer (ʻIARCʼ), nearly 1.7 million women were diagnosed with breast cancer, with 522,000 related deaths: An increase in the incidence of breast cancer and associated mortality by nearly 18% from 2008. Metastasis is the final step in breast cancer progression, and represents the most common cause of mortality in patients with breast cancer. Therefore, a search for low-toxicity, safe and effective anti-breast cancer drugs in the form of natural compounds has become an intense focus of research. Baicalein, a widely used Chinese herbal medicine, has extensive antitumor activity. The present review briefly describes the research that has been performed on the association between baicalein and breast cancer metastasis, and further illustrates the influence of baicalein on the underlying mechanisms of breast cancer metastasis, adding a novel theory basis for baicalein antitumor research. In conclusion, baicalein may represent a promising target for the prevention and therapy of breast cancer.

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Dimethylarginine dimethylaminohydrolase 2, a newly identified mitochondrial protein modulating nitric oxide synthesis in normal human chondrocytes

Cillero‐Pastor

Mateos

Fernández-López

et al. 2011

Arthritis & Rheumatism

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Objective. The mitochondrion is known to be important to chondrocyte survival. This study was undertaken to analyze protein expression profiles in chondrocyte mitochondria that are affected by interleukin-1␤ (IL-1␤).Methods. Normal human chondrocytes were isolated from knee cartilage obtained at autopsy from subjects with no history of joint disease. Cells were incubated for 48 hours with or without IL-1␤ (5 ng/ml). Proteins were separated by 2-dimensional electrophoresis and stained with Sypro Ruby, Coomassie brilliant blue, or silver. Qualitative and quantitative analyses were carried out using PDQuest software. Proteins were identified by mass spectrometry using matrix-assisted laser desorption ionization-time-of-flight/time-of-flight technology. The proteomic results were validated by real-time polymerase chain reaction, Western blotting, and microscopy. Nitric oxide (NO) was quantified using Griess reagent.Results. Comparative analysis revealed differential expression of signal transduction proteins that regulate cytoskeleton, transcription, metabolic, and stress-related pathways. In total extracts, dimethylarginine dimethylaminohydrolase 2 (DDAH-2) did not show any change in expression after stimulation with IL-1␤.However, in mitochondrial extracts, DDAH-2 expression was significantly increased after exposure to IL-1␤. Conventional immunofluorescence and confocal microscopy revealed the presence of DDAH-2 in the mitochondria of IL-1␤-stimulated chondrocytes. These results were reproducible in cartilage explants treated with IL-1␤. In addition, we demonstrated that inhibition of the expression of DDAH-2, as well as interruption of its translocation to the mitochondria, reduced the NO production induced by IL-1␤. DDAH-2 protein expression was higher in osteoarthritic (OA) cartilage than in normal cartilage.Conclusion. In the present study, the presence of DDAH-2 in normal human chondrocytes and cartilage was identified for the first time. DDAH-2 could play an important role in IL-1␤-induced NO production and in OA pathogenesis.

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

Cited by 101 publications

References 50 publications

Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer

Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer

Latest research progress in the correlation between baicalein and breast cancer invasion and metastasis

Dimethylarginine dimethylaminohydrolase 2, a newly identified mitochondrial protein modulating nitric oxide synthesis in normal human chondrocytes

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