Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) is an active compound of many laxative herbal drugs. The present study aimed to determine the effects of emodin on cytochrome P450 (P450)-dependent monooxygenases of human lung adenocarcinoma CL5 cells. Treatment of CL5 cells with 100 microM emodin for 24 h induced benzo[a]pyrene hydroxylation, 7-ethoxyresorufin O-deethylation, and 7-ethoxycoumarin O-deethylation activities of S9 fractions. Immunoblot analysis of CL5 S9 proteins revealed that emodin induced proteins immunorelated to P450s 1A1 and 1B1. Northern blot analysis of total cellular RNA showed that emodin induced P450s 1A1 and 1B1 mRNA levels in CL5 cells. These inductive effects on P450 monooxygenase activity, protein, and mRNA were concentration- and time-dependent. Addition of emodin to CL5 cell microM S9 inhibited its 7-ethoxycoumarin O-deethylation activity. Treatment of CL5 cells with 10 microM 3-methylcholanthrene for 24 h induced monooxygenase activity and P450s 1A1 and 1B1 proteins and mRNA levels. Treatment of the lung cells with 100 microM emodin or purpurin (1,2,4-trihydroxyanthraquinone) for 24 h produced greater induction of P450s 1A1 and 1B1 mRNA than did anthraflavic acid (2,6-dihydroxyanthraquinone) or anthraquinone. The emodin treatment induced P450s 1A1 and 1B1 mRNA in human lung carcinoma NCI-H322 and breast cancer MCF-7 cells. Emodin induced P450 1A1, but not 1B1, mRNA in human hepatoma HepG2 cells. The present study demonstrates that emodin is an inducer of P450s 1A1 and 1B1 protein and mRNA in human lung adenocarcinoma CL5 cells. Modulation of P450 by emodin may be an important factor affecting metabolism and toxicity of the hydroxyanthraquinone in humans.
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PMID:Induction of cytochromes P450 1A1 and 1B1 by emodin in human lung adenocarcinoma cell line CL5. 1150 33

Emodin, a tyrosine kinase inhibitor, is a natural anthraquinone derivative found in the roots and rhizomes of numerous plants; it exhibits an anticancer effect on many malignancies. The most important chemotherapeutic agent for patients with advanced non-small cell lung cancer (NSCLC) is a platinum-containing compound such as cisplatin or carboplatin. The molecular mechanism underlying decreased NSCLC cell viability after treatment with emodin and cisplatin is unclear. Therefore, the aim of this study was to assess the cytotoxic effect of combined emodin and cisplatin on NSCLC cell lines and to clarify underlying molecular mechanisms. Exposure of human NSCLC cells to emodin decreased cisplatin-elicited ERK1/2 activation and ERCC1 protein induction by increasing instability of ERCC1 protein. Cisplatin alone did not affect expression of ERCC1 mRNA. However, emodin alone or combined with cisplatin significantly decreased expression of ERCC1 mRNA levels. Enhancement of ERK1/2 activation by transfection with constitutively active MKK1/2 (MKK1/2-CA) vector increased ERCC1 protein levels and protein stability, as well as increasing viability of NSCLC cells treated with emodin and cisplatin. In contrast, blocking ERK1/2 activation by U0126 (an MKK1/2 inhibitor) decreased cisplatin-elicited ERCC1 expression and enhanced cisplatin-induced cytotoxicity. Depletion of endogenous ERCC1 expression by si-ERCC1 RNA transfection significantly enhanced cisplatin's cytotoxic effect. In conclusion, ERCC1 protein protects NSCLC cells from synergistic cytotoxicity induced by emodin and platinum agents. Further investigation of combined emodin and cisplatin may lead to novel therapy in the future for NSCLC through down-regulating expression of ERCC1.
Lung Cancer 2010 Aug
PMID:Emodin enhances cisplatin-induced cytotoxicity via down-regulation of ERCC1 and inactivation of ERK1/2. 1996 80