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Luteolin exerts an anticancer effect on NCI-H460 human non-small cell lung cancer cells through the induction of Sirt1-mediated apoptosis.

ABSTRACT: 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.

SUBMITTER: Ma L

PROVIDER: S-EPMC4526059 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Luteolin exerts an anticancer effect on NCI-H460 human non-small cell lung cancer cells through the induction of Sirt1-mediated apoptosis.

Ma Liping L Peng Hongjun H Li Kunsheng K Zhao Runrun R Li Li L Yu Yilong Y Wang Xiaoming X Han Zhifeng Z

Molecular medicine reports 20150618 3

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/flu ...[more]

PMID: 26096576

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Project description:In both males and females, lung cancer is one of the most lethal cancers worldwide and accounts for >30% of cancer-related deaths. Despite advances in biomarker analysis and tumor characterization, there remains a need to find suitable biomarker antigen targets for treatment in late-stage lung cancer. Previous research on the salvage pathway enzyme TK1 shows a unique relationship with cancer patients as serum levels are raised according to cancer grade. To expand this analysis, the other salvage pathway enzymes were evaluated for possible upregulation within lung cancer. Adenine phosphoribosyltransferase, deoxycytidine kinase, and hypoxanthine guanine phosphoribosyltransferase (HPRT) were assessed for their presentation on two non-small-cell lung cancer cell lines NCI-H460 and A549. In the present study, we show that deoxycytidine kinase and adenine phosphoribosyltransferase have no significant relationship with the membrane of NCI-H460 cells. However, we found significant localization of HPRT to the membrane of NCI-H460 and A549 cells. When treated with anti-HPRT antibodies, the average fluorescence of the cell population increased by 24.3% and 12.9% in NCI-H460 and A549 cells, respectively, in comparison with controls. To ensure that expression was not attributed to cytoplasmic HPRT, confocal microscopy was performed to visualize HPRT binding on the plasma membrane. After staining NCI-H460 cells treated with both fluorescent antibodies and a membrane-specific dye, we observed direct overlap between HPRT and the membrane of the cancer cells. Additionally, gold-conjugated antibodies were used to label and quantify the amount of HPRT on the cell surface using scanning electron microscopy and energy-dispersive analysis X-ray. Further confirming HPRT presence, the gold weight percentage of the sample increased significantly when NCI-H460 cells were exposed to HPRT antibody (P=0.012) in comparison with isotype controls. Our results show that HPRT is localized on the surface of these non-small-cell lung cancer cell lines.

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Luteolin exerts an anticancer effect on NCI-H460 human non-small cell lung cancer cells through the induction of Sirt1-mediated apoptosis.

Publications

Luteolin exerts an anticancer effect on NCI-H460 human non-small cell lung cancer cells through the induction of Sirt1-mediated apoptosis.

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