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Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways
Pratheeshkumar P.1,2; Son Y.-O.1,2; Divya S.P.1,2; Roy R.V.1,2; Hitron J.A.1,2; Wang L.1,2; Kim D.2; Dai J.2; Asha P.3; Zhang Z.2; Wang Y.4; Shi X.1,2
2014
Source PublicationToxicology and Applied Pharmacology
ISSN0041008X
Volume281Issue:2Pages:230
Abstract

Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Inhibition of metal induced carcinogenesis by a dietary antioxidant is a novel approach. Luteolin, a natural dietary flavonoid found in fruits and vegetables, possesses potent antioxidant and anti-inflammatory activity. We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5. μM) showed a drastic increase in ROS generation, NADPH oxidase (NOX) activation, lipid peroxidation, and glutathione depletion, which were significantly inhibited by the treatment with luteolin in a dose dependent manner. Treatment with luteolin decreased AP-1, HIF-1α, COX-2, and iNOS promoter activity induced by Cr(VI) in BEAS-2B cells. In addition, luteolin protected BEAS-2B cells from malignant transformation induced by chronic Cr(VI) exposure. Moreover, luteolin also inhibited the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and VEGF in chronic Cr(VI) exposed BEAS-2B cells. Western blot analysis showed that luteolin inhibited multiple gene products linked to survival (Akt, Fak, Bcl-2, Bcl-xL), inflammation (MAPK, NF-κB, COX-2, STAT-3, iNOS, TNF-α) and angiogenesis (HIF-1α, VEGF, MMP-9) in chronic Cr(VI) exposed BEAS-2B cells. Nude mice injected with BEAS-2B cells chronically exposed to Cr(VI) in the presence of luteolin showed reduced tumor incidence compared to Cr(VI) alone treated group. Overexpression of catalase (CAT) or SOD2, eliminated Cr(VI)-induced malignant transformation. Overall, our results indicate that luteolin protects BEAS-2B cells from Cr(VI)-induced carcinogenesis by scavenging ROS and modulating multiple cell signaling mechanisms that are linked to ROS. Luteolin, therefore, serves as a potential chemopreventive agent against Cr(VI)-induced carcinogenesis. © 2014 Elsevier Inc.

KeywordAngiogenesis Carcinogenesis Hexavalent Chromium Inflammation Luteolin
DOIhttp://doi.org/10.1016/j.taap.2014.10.008
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy ; Toxicology
WOS SubjectPharmacology & Pharmacy ; Toxicology
WOS IDWOS:000346227000009
The Source to ArticleScopus
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Cited Times [WOS]:40   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorShi X.
Affiliation1.Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA
2.Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA
3.National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Cochin, India
4.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
Recommended Citation
GB/T 7714
Pratheeshkumar P.,Son Y.-O.,Divya S.P.,et al. Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways[J]. Toxicology and Applied Pharmacology,2014,281(2):230.
APA Pratheeshkumar P..,Son Y.-O..,Divya S.P..,Roy R.V..,Hitron J.A..,...&Shi X..(2014).Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways.Toxicology and Applied Pharmacology,281(2),230.
MLA Pratheeshkumar P.,et al."Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways".Toxicology and Applied Pharmacology 281.2(2014):230.
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