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Emodin regulates cell cycle of non-small lung cancer (NSCLC) cells through hyaluronan synthase 2 (HA2)-HA-CD44/receptor for hyaluronic acid-mediated motility (RHAMM) interaction-dependent signaling pathway

BACKGROUND: Non-small cell lung cancers (NSCLC) account for most cases of lung cancer. More effort is needed to research new drug and combination therapies for this disease. An anthraquinone derivative, emodin shows anticancer potency. We hypothesis that emodin suppresses lung cancer cells through h...

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Autores principales: Li, Mingzhu, Jin, Shengbo, Cao, Yang, Xu, Jian, Zhu, Shendong, Li, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789699/
https://www.ncbi.nlm.nih.gov/pubmed/33407495
http://dx.doi.org/10.1186/s12935-020-01711-z
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author Li, Mingzhu
Jin, Shengbo
Cao, Yang
Xu, Jian
Zhu, Shendong
Li, Zheng
author_facet Li, Mingzhu
Jin, Shengbo
Cao, Yang
Xu, Jian
Zhu, Shendong
Li, Zheng
author_sort Li, Mingzhu
collection PubMed
description BACKGROUND: Non-small cell lung cancers (NSCLC) account for most cases of lung cancer. More effort is needed to research new drug and combination therapies for this disease. An anthraquinone derivative, emodin shows anticancer potency. We hypothesis that emodin suppresses lung cancer cells through hyaluronan (HA) synthase 2-HA-CD44/receptor for hyaluronic acid-mediated motility (RHAMM) interaction-dependent signaling pathway mediated cell cycle regulation. METHODS: We tested the effect of emodin on viability, apoptosis, and HA secretion of 5 NSCLC cell lines. We used NSCLC cells A549 for two rounds of knockdown study: (1) knocking down either the synthases (HAS2 and HAS3) or the receptors (CD44 and RHAMM); (2) knocking down either HAS2 or HAS3. Then determined the effect of emodin on viability, HA secretion, cell cycle, and expression of cyclin proteins. RESULTS: Emodin suppressed viability and HA secretion of all 5 NSCLC cell lines except for HA secretion of H460. Emodin had a slight apoptosis induction effect on all cell lines and was not different among cell lines. The knockdown of either the synthases or the receptors blocked emodin effects on viability while the knockdown of HAS2 block emodin effects but not HAS3. Emodin increased cells in the G1/G0 phase, and decreased cells in the S and G2/M phase by down-regulating cyclin A and B and up-regulating cyclin C, D, and E. HAS2 knockdown blocked the effects of emodin on the cell cycle. CONCLUSIONS: This study demonstrated that emodin regulates the cell cycle of NSCLC cells through the HAS2-HA-CD44/RHAMM interaction-dependent signaling pathway.
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spelling pubmed-77896992021-01-07 Emodin regulates cell cycle of non-small lung cancer (NSCLC) cells through hyaluronan synthase 2 (HA2)-HA-CD44/receptor for hyaluronic acid-mediated motility (RHAMM) interaction-dependent signaling pathway Li, Mingzhu Jin, Shengbo Cao, Yang Xu, Jian Zhu, Shendong Li, Zheng Cancer Cell Int Primary Research BACKGROUND: Non-small cell lung cancers (NSCLC) account for most cases of lung cancer. More effort is needed to research new drug and combination therapies for this disease. An anthraquinone derivative, emodin shows anticancer potency. We hypothesis that emodin suppresses lung cancer cells through hyaluronan (HA) synthase 2-HA-CD44/receptor for hyaluronic acid-mediated motility (RHAMM) interaction-dependent signaling pathway mediated cell cycle regulation. METHODS: We tested the effect of emodin on viability, apoptosis, and HA secretion of 5 NSCLC cell lines. We used NSCLC cells A549 for two rounds of knockdown study: (1) knocking down either the synthases (HAS2 and HAS3) or the receptors (CD44 and RHAMM); (2) knocking down either HAS2 or HAS3. Then determined the effect of emodin on viability, HA secretion, cell cycle, and expression of cyclin proteins. RESULTS: Emodin suppressed viability and HA secretion of all 5 NSCLC cell lines except for HA secretion of H460. Emodin had a slight apoptosis induction effect on all cell lines and was not different among cell lines. The knockdown of either the synthases or the receptors blocked emodin effects on viability while the knockdown of HAS2 block emodin effects but not HAS3. Emodin increased cells in the G1/G0 phase, and decreased cells in the S and G2/M phase by down-regulating cyclin A and B and up-regulating cyclin C, D, and E. HAS2 knockdown blocked the effects of emodin on the cell cycle. CONCLUSIONS: This study demonstrated that emodin regulates the cell cycle of NSCLC cells through the HAS2-HA-CD44/RHAMM interaction-dependent signaling pathway. BioMed Central 2021-01-06 /pmc/articles/PMC7789699/ /pubmed/33407495 http://dx.doi.org/10.1186/s12935-020-01711-z Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Li, Mingzhu
Jin, Shengbo
Cao, Yang
Xu, Jian
Zhu, Shendong
Li, Zheng
Emodin regulates cell cycle of non-small lung cancer (NSCLC) cells through hyaluronan synthase 2 (HA2)-HA-CD44/receptor for hyaluronic acid-mediated motility (RHAMM) interaction-dependent signaling pathway
title Emodin regulates cell cycle of non-small lung cancer (NSCLC) cells through hyaluronan synthase 2 (HA2)-HA-CD44/receptor for hyaluronic acid-mediated motility (RHAMM) interaction-dependent signaling pathway
title_full Emodin regulates cell cycle of non-small lung cancer (NSCLC) cells through hyaluronan synthase 2 (HA2)-HA-CD44/receptor for hyaluronic acid-mediated motility (RHAMM) interaction-dependent signaling pathway
title_fullStr Emodin regulates cell cycle of non-small lung cancer (NSCLC) cells through hyaluronan synthase 2 (HA2)-HA-CD44/receptor for hyaluronic acid-mediated motility (RHAMM) interaction-dependent signaling pathway
title_full_unstemmed Emodin regulates cell cycle of non-small lung cancer (NSCLC) cells through hyaluronan synthase 2 (HA2)-HA-CD44/receptor for hyaluronic acid-mediated motility (RHAMM) interaction-dependent signaling pathway
title_short Emodin regulates cell cycle of non-small lung cancer (NSCLC) cells through hyaluronan synthase 2 (HA2)-HA-CD44/receptor for hyaluronic acid-mediated motility (RHAMM) interaction-dependent signaling pathway
title_sort emodin regulates cell cycle of non-small lung cancer (nsclc) cells through hyaluronan synthase 2 (ha2)-ha-cd44/receptor for hyaluronic acid-mediated motility (rhamm) interaction-dependent signaling pathway
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789699/
https://www.ncbi.nlm.nih.gov/pubmed/33407495
http://dx.doi.org/10.1186/s12935-020-01711-z
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