Vernolide-A, a sesquiterpene lactone from<i>Vernonia cinerea,</i>induces apoptosis in B16F-10 melanoma cells by modulating p53 and caspase-3 gene expressions and regulating NF-κB-mediated bcl-2 activation

Pratheeshkumar, Poyil; Kuttan, Girija

doi:10.3109/01480545.2010.520017

Cited by 32 publications

(19 citation statements)

References 43 publications

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“…Upon activation, IκB becomes phosphorylated, a process that targets it for ubiquitination and degradation by proteasomes. This activation results the rapid translocation of NF-κB to the nucleus, where it binds to κB binding sites in the promoter region of target genes, and induces the transcription of pro-inflammatory mediators, including iNOS, COX-2, TNF-α, IL-6 and others (Perkins, 1997; Pratheeshkumar and Kuttan, 2011c; Wang et al , 2012). Previous studies have shown that NF-κB activation occurs in responses to several environmental carcinogens (Ding et al , 2006; Ouyang et al , 2007).…”

Section: Discussionmentioning

confidence: 99%

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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

Pratheeshkumar¹,

Son²,

Divya³

et al. 2014

Toxicology and Applied Pharmacology

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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.

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Section: Discussionmentioning

confidence: 99%

“…Active mitochondrial dehydrogenases in living cells metabolize MTT to a purple formazan dye, which is measured photometrically at 570 nm using a spectrophotometer as described previously (Pratheeshkumar and Kuttan, 2011c). …”

Section: Methodsmentioning

confidence: 99%

Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

Pratheeshkumar¹,

Son²,

Divya³

et al. 2014

Toxicology and Applied Pharmacology

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“…Recently, many sesquiterpene lactone compounds have been shown to induce apoptosis in various cancer cell lines through inhibition of NF-jB activation (31)(32)(33). Inhibition of TNFainduced NF-jB activation results in apoptosis by recruiting caspase 8, indicating that TNFa can induce either prosurvival or apoptotic pathway (34).…”

Section: Discussionmentioning

confidence: 99%

Alantolactone induces apoptosis in glioblastoma cells via GSH depletion, ROS generation, and mitochondrial dysfunction

et al. 2012

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Glioblastoma multiforme (GBM) is the most malignant and aggressive primary brain tumor in adults. Despite concerted efforts to improve current therapies, the prognosis of glioblastoma remains very poor. Alantolactone, a sesquiterpene lactone compound, has been reported to exhibit antifungal, antibacteria, antihelminthic, and anticancer properties. In this study, we found that alantolactone effectively inhibits growth and triggers apoptosis in glioblastoma cells in a time‐ and dose‐dependent manner. The alantolactone‐induced apoptosis was found to be associated with glutathione (GSH) depletion, reactive oxygen species (ROS) generation, mitochondrial transmembrane potential dissipation, cardiolipin oxidation, upregulation of p53 and Bax, downregulation of Bcl‐2, cytochrome c release, activation of caspases (caspase 9 and 3), and cleavage of poly (ADP‐ribose) polymerase. This alantolactone‐induced apoptosis and GSH depletion were effectively inhibited or abrogated by a thiol antioxidant, N‐acetyl‐L‐cysteine, whereas other antioxidant (polyethylene glycol (PEG)‐catalase and PEG‐superoxide‐dismutase) did not prevent apoptosis and GSH depletion. Alantolactone treatment inhibited the translocation of NF‐κB into nucleus; however, NF‐κB inhibitor, SN50 failed to potentiate alantolactone‐induced apoptosis indicating that alantolactone induces NF‐κB‐independent apoptosis in glioma cells. These findings suggest that the sensitivity of tumor cells to alantolactone appears to results from GSH depletion and ROS production. Furthermore, our in vivo toxicity study demonstrated that alantolactone did not induce significant hepatotoxicity and nephrotoxicity in mice. Therefore, alantolactone may become a potential lead compound for future development of antiglioma therapy. © © 2012 IUBMB Life, 64(9): 783–794, 2012

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“…(Pratheeshkumar and Kuttan, 2011b). Aberrant, sustained activation of NF-κB has been reported in numerous tumors and was implicated in various stages of photocarcinogenesis (Khan et al , 2012; Wang et al , 2012).…”

Section: Discussionmentioning

confidence: 99%

Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin

Pratheeshkumar¹,

Son²,

Wang³

et al. 2014

Toxicology and Applied Pharmacology

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Skin cancer is one of the most commonly diagnosed cancers in the United States. Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Cyanidin-3-Glucoside (C3G), a member of the anthocyanin family, is present in various vegetables and fruits especially in edible berries, and displays potent antioxidant and anticarcinogenic properties. In this study, we have assessed the in vivo effects of C3G on UVB irradiation induced chronic inflammatory responses in SKH-1 hairless mice, a well-established model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB-induced skin damage and inflammation in SKH-1 hairless mice. Our results indicate that C3G inhibited glutathione depletion, lipid peroxidation and myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6 and TNF-α, associated with cutaneous inflammation. Likewise, UVB-induced inflammatory responses were diminished by C3G as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE2 and iNOS levels, which are well-known key mediators of inflammation and cancer. Treatment with C3G inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mice skin. Immunofluorescence assay revealed that topical application of C3G inhibited the expression of 8-hydroxy-2′-deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB exposed mouse skin. Collectively, these data indicates that C3G can provide substantial protection against the adverse effects of UVB radiation by modulating UVB-induced MAP kinase and NF-κB signaling pathways.

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Vernolide-A, a sesquiterpene lactone fromVernonia cinerea,induces apoptosis in B16F-10 melanoma cells by modulating p53 and caspase-3 gene expressions and regulating NF-κB-mediated bcl-2 activation

Cited by 32 publications

References 43 publications

Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

Alantolactone induces apoptosis in glioblastoma cells via GSH depletion, ROS generation, and mitochondrial dysfunction

Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin

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