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Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer
Luteolin, an active component of traditional Chinese medicine, exhibits potential for anti-tumor proliferation; however, the molecular events occurring in such process and the signal transduction pathways involved are currently unknown. Our group previously reported that luteolin inhibited prolifera...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530081/ https://www.ncbi.nlm.nih.gov/pubmed/28789432 http://dx.doi.org/10.3892/ol.2017.6380 |
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author | Lu, Xueying Li, Yanhong Li, Xiaobo Aisa, Haji Akber |
author_facet | Lu, Xueying Li, Yanhong Li, Xiaobo Aisa, Haji Akber |
author_sort | Lu, Xueying |
collection | PubMed |
description | Luteolin, an active component of traditional Chinese medicine, exhibits potential for anti-tumor proliferation; however, the molecular events occurring in such process and the signal transduction pathways involved are currently unknown. Our group previously reported that luteolin inhibited proliferation and induced apoptosis in the gastric cancer cell line BGC-823. The aim of the present study was to investigate the mechanism by which the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling pathways regulate the apoptosis in vitro of BGC-823 cells following treatment with luteolin. It was observed that luteolin induced apoptosis through the intrinsic pathway by increasing the levels of caspase-3, caspase-9 and cytochrome c, and the ratio of B-cell lymphoma (Bcl)-2 associated X protein (Bax) to Bcl-2. Luteolin suppressed the phosphorylation of extracellular signal-regulated kinase in the MAPK signaling pathway, as well as suppressing the phosphorylation of AKT, PI3K and mechanistic target of rapamycin in the PI3K signaling pathway. In addition, luteolin combined with LY294002 markedly increased the Bax/Bcl-2 ratio, while when combined with U0126, luteolin had less effects on the Bax/Bcl-2 ratio compared with luteolin treatment alone, suggesting that both the MAPK and PI3K signaling pathways are involved in the apoptosis induced by luteolin. Furthermore, luteolin attenuated the MAPK and PI3K signaling pathways by increasing the expression of specific dual-specificity phosphatases and decreasing the expression of chemokine (C-X-C motif) ligand 16 at the messenger RNA level, respectively. Taken together, the present results demonstrate that luteolin is a potential chemotherapeutic agent against gastric cancer by exerting a dual inhibition on the MAPK and PI3K signaling pathways. |
format | Online Article Text |
id | pubmed-5530081 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-55300812017-08-07 Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer Lu, Xueying Li, Yanhong Li, Xiaobo Aisa, Haji Akber Oncol Lett Articles Luteolin, an active component of traditional Chinese medicine, exhibits potential for anti-tumor proliferation; however, the molecular events occurring in such process and the signal transduction pathways involved are currently unknown. Our group previously reported that luteolin inhibited proliferation and induced apoptosis in the gastric cancer cell line BGC-823. The aim of the present study was to investigate the mechanism by which the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling pathways regulate the apoptosis in vitro of BGC-823 cells following treatment with luteolin. It was observed that luteolin induced apoptosis through the intrinsic pathway by increasing the levels of caspase-3, caspase-9 and cytochrome c, and the ratio of B-cell lymphoma (Bcl)-2 associated X protein (Bax) to Bcl-2. Luteolin suppressed the phosphorylation of extracellular signal-regulated kinase in the MAPK signaling pathway, as well as suppressing the phosphorylation of AKT, PI3K and mechanistic target of rapamycin in the PI3K signaling pathway. In addition, luteolin combined with LY294002 markedly increased the Bax/Bcl-2 ratio, while when combined with U0126, luteolin had less effects on the Bax/Bcl-2 ratio compared with luteolin treatment alone, suggesting that both the MAPK and PI3K signaling pathways are involved in the apoptosis induced by luteolin. Furthermore, luteolin attenuated the MAPK and PI3K signaling pathways by increasing the expression of specific dual-specificity phosphatases and decreasing the expression of chemokine (C-X-C motif) ligand 16 at the messenger RNA level, respectively. Taken together, the present results demonstrate that luteolin is a potential chemotherapeutic agent against gastric cancer by exerting a dual inhibition on the MAPK and PI3K signaling pathways. D.A. Spandidos 2017-08 2017-06-14 /pmc/articles/PMC5530081/ /pubmed/28789432 http://dx.doi.org/10.3892/ol.2017.6380 Text en Copyright: © Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Lu, Xueying Li, Yanhong Li, Xiaobo Aisa, Haji Akber Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer |
title | Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer |
title_full | Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer |
title_fullStr | Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer |
title_full_unstemmed | Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer |
title_short | Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer |
title_sort | luteolin induces apoptosis in vitro through suppressing the mapk and pi3k signaling pathways in gastric cancer |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530081/ https://www.ncbi.nlm.nih.gov/pubmed/28789432 http://dx.doi.org/10.3892/ol.2017.6380 |
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