| Description: |
Luteolin is a non-selective phisphodiesterase PDE inhibitor for PDE1-5 with Ki of 15.0 μM, 6.4 μM, 13.9 μM, 11.1 μM and 9.5 μM, respectively. Luteolin has anti-oxidant, anti-inflammation, anti-allergy anti-myocardial ischemia-reperfusion injury, and anticancer, has been used in Chinese traditional medicine for treating various diseases such as hypertension, inflammatory disorders, and cancer. Luteolin inhibits NF-κB, and inhibits interleukin (IL)-1β function induction of the inflammation biomarker cyclooxygenase (COX)-2. |
| In vitro: |
| Biochim Biophys Acta. 2015 Jan;1853(1):126-35. | | Biphasic effects of luteolin on interleukin-1β-induced cyclooxygenase-2 expression in glioblastoma cells.[Pubmed: 25409926] | Success in developing therapeutic approaches to target brain tumor-associated inflammation in patients has been limited. Given that the inflammatory microenvironment is a hallmark signature of solid tumor development, anti-inflammatory targeting strategies have been envisioned as preventing glioblastoma initiation or progression.
Consumption of foods from plant origin is associated with reduced risk of developing cancers, a chemopreventive effect that is, in part, attributed to their high content of phytochemicals with potent anti-inflammatory properties.
METHODS AND RESULTS:
We explored whether luteolin, a common flavonoid in many types of plants, may inhibit interleukin (IL)-1β function induction of the inflammation biomarker cyclooxygenase (COX)-2. We found that IL-1β triggered COX-2 expression in U-87 glioblastoma cells and synergized with luteolin to potentiate or inhibit that induction in a biphasic manner. Luteolin pretreatment of cells inhibited IL-1β-mediated phosphorylation of inhibitor of κB, nuclear transcription factor-κB (NF-κB) p65, extracellular signal-regulated kinase-1/2, and c-Jun amino-terminal kinase in a concentration-dependent manner. Luteolin also inhibited AKT phosphorylation and survivin expression, while it triggered both caspase-3 cleavage and expression of glucose-regulated protein 78. These effects were all potentiated by IL-1β, in part through increased nuclear translocation of NF-κB p65. Finally, luteolin was able to reduce IL-1 receptor gene expression, and treatment with IL-1 receptor antagonist or gene silencing of IL-1 receptor prevented IL-1β/luteolin-induced COX-2 expression.
CONCLUSIONS:
Our results document a novel adaptive cellular response to luteolin, which triggers anti-survival and anti-inflammatory mechanisms that contribute to the chemopreventive properties of this diet-derived molecule. | | Toxicol Appl Pharmacol. 2014 Dec 1;281(2):230-41. | | Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways.[Pubmed: 25448439] | 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.
METHODS AND RESULTS:
We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5μM) 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.
CONCLUSIONS:
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. | | Mol Med Rep . 2015 Sep;12(3):4196-4202. | | Luteolin exerts an anticancer effect on NCI-H460 human non-small cell lung cancer cells through the induction of Sirt1-mediated apoptosis[Pubmed: 26096576] | | Luteolin is a falconoid compound, which exhibits anticancer properties, however, its contribution to Sirt1-mediated apoptosis in human non-small cell lung cancer remains to be elucidated. The present study confirmed that the anticancer effect of luteolin on NCI‑H460 cells was through Sirt1‑mediated apoptosis. The NCI‑H460 cells were treated with different concentrations of luteolin, and a 3‑(4,5‑dimethyl‑2‑thiazolyl)‑2,5‑diphnyl‑2H‑tetrazolium bromide assay, cell cycle analysis and annexin‑V/fluorescein isothiocyanate and propidium double staining were performed to assess the apoptotic effect of luteolin. Wound healing and Transwell assays were performed to confirm the inhibition of NCI‑H460 cell migration. The protein levels of Sirt1 were knocked down in the NCI‑H460 cells using a lentivirus to further investigate the role of this protein, and the expression levels of the apoptotic associated proteins, Bad, Bcl‑2, Bax, caspase‑3 and Sirt1, were measured using western blotting. The results of the present study demonstrated that luteolin exerted an anticancer effect against NCI‑H460 cells through Sirt1‑mediated apoptosis and the inhibition of cell migration. |
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| In vivo: |
| Curr Cancer Drug Targets. 2008 Nov;8(7):634-46. | | Luteolin, a flavonoid with potential for cancer prevention and therapy.[Pubmed: 18991571 ] | Luteolin, 3',4',5,7-tetrahydroxyflavone, is a common flavonoid that exists in many types of plants including fruits, vegetables, and medicinal herbs. Plants rich in luteolin have been used in Chinese traditional medicine for treating various diseases such as hypertension, inflammatory disorders, and cancer. Having multiple biological effects such as anti-inflammation, anti-allergy and anticancer, luteolin functions as either an antioxidant or a pro-oxidant biochemically. The biological effects of luteolin could be functionally related to each other. For instance, the anti-inflammatory activity may be linked to its anticancer property. Luteolin's anticancer property is associated with the induction of apoptosis, and inhibition of cell proliferation, metastasis and angiogenesis. Furthermore, luteolin sensitizes cancer cells to therapeutic-induced cytotoxicity through suppressing cell survival pathways such as phosphatidylinositol 3'-kinase (PI3K)/Akt, nuclear factor kappa B (NF-kappaB), and X-linked inhibitor of apoptosis protein (XIAP), and stimulating apoptosis pathways including those that induce the tumor suppressor p53. These observations suggest that luteolin could be an anticancer agent for various cancers. Furthermore, recent epidemiological studies have attributed a cancer prevention property to luteolin.
CONCLUSIONS:
In this review, we summarize the progress of recent research on luteolin, with a particular focus on its anticancer role and molecular mechanisms underlying this property of luteolin. |
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