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Suchilactone inhibits the growth of acute myeloid leukaemia by inactivating SHP2

CONTEXT: Suchilactone, a lignan compound extracted from Monsonia angustifolia E.Mey. ex A.Rich. (Geraniaceae), has little research on pharmacological activity; whether suchilactone has inhibitory effect on acute myeloid leukaemia (AML) is unclear. OBJECTIVE: To investigate the antitumor effect of su...

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Autores principales: Wu, Jingjing, Deng, Yuan, Zhang, Xin, Ma, Jingjing, Zheng, Xinqi, Chen, Yue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725822/
https://www.ncbi.nlm.nih.gov/pubmed/34962431
http://dx.doi.org/10.1080/13880209.2021.2017467
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author Wu, Jingjing
Deng, Yuan
Zhang, Xin
Ma, Jingjing
Zheng, Xinqi
Chen, Yue
author_facet Wu, Jingjing
Deng, Yuan
Zhang, Xin
Ma, Jingjing
Zheng, Xinqi
Chen, Yue
author_sort Wu, Jingjing
collection PubMed
description CONTEXT: Suchilactone, a lignan compound extracted from Monsonia angustifolia E.Mey. ex A.Rich. (Geraniaceae), has little research on pharmacological activity; whether suchilactone has inhibitory effect on acute myeloid leukaemia (AML) is unclear. OBJECTIVE: To investigate the antitumor effect of suchilactone and its mechanism in AML. MATERIALS AND METHODS: The effects of suchilactone on cell growth were detected by CCK-8 and flow cytometry. Network pharmacology was conducted to explore target of suchilactone. Gene expression was detected by western blot and RT-PCR. SHI-1 cells (1 × 10(6) cell per mouse) were subcutaneously inoculated into the female SCID mice. Suchilactone (15 and 30 mg/kg) was dissolved in PBS with 0.5% carboxymethylcellulose sodium and administered (i.g.) to mice once a day for 19 days, while the control group received PBS with 0.5% carboxymethylcellulose sodium. Tumour tissues were stained with Ki-67 and TUNEL. RESULTS: Suchilactone exerted an effective inhibition on the growth of SHI-1 cells with IC(50) of 17.01 μM. Then, we found that suchilactone binds to the SHP2 protein and inhibits its activation, and suchilactone interacted with SHP2 to inhibit cell proliferation and promote cell apoptosis via blocking the activation of SHP2. Moreover, Suchilaction inhibited tumour growth of AML xenografts in mice, as the tumour weight decreased from 0.618 g (control) to 0.35 g (15 mg/kg) and 0.258 g (30 mg/kg). Suchilactone inhibited Ki-67 expression and increased TUNEL expression in tumour tissue. DISCUSSION AND CONCLUSIONS: Our study is the first to demonstrate suchilactone inhibits AML growth, suggesting that suchilactone is a candidate drug for the treatment of AML.
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spelling pubmed-87258222022-01-05 Suchilactone inhibits the growth of acute myeloid leukaemia by inactivating SHP2 Wu, Jingjing Deng, Yuan Zhang, Xin Ma, Jingjing Zheng, Xinqi Chen, Yue Pharm Biol Research Article CONTEXT: Suchilactone, a lignan compound extracted from Monsonia angustifolia E.Mey. ex A.Rich. (Geraniaceae), has little research on pharmacological activity; whether suchilactone has inhibitory effect on acute myeloid leukaemia (AML) is unclear. OBJECTIVE: To investigate the antitumor effect of suchilactone and its mechanism in AML. MATERIALS AND METHODS: The effects of suchilactone on cell growth were detected by CCK-8 and flow cytometry. Network pharmacology was conducted to explore target of suchilactone. Gene expression was detected by western blot and RT-PCR. SHI-1 cells (1 × 10(6) cell per mouse) were subcutaneously inoculated into the female SCID mice. Suchilactone (15 and 30 mg/kg) was dissolved in PBS with 0.5% carboxymethylcellulose sodium and administered (i.g.) to mice once a day for 19 days, while the control group received PBS with 0.5% carboxymethylcellulose sodium. Tumour tissues were stained with Ki-67 and TUNEL. RESULTS: Suchilactone exerted an effective inhibition on the growth of SHI-1 cells with IC(50) of 17.01 μM. Then, we found that suchilactone binds to the SHP2 protein and inhibits its activation, and suchilactone interacted with SHP2 to inhibit cell proliferation and promote cell apoptosis via blocking the activation of SHP2. Moreover, Suchilaction inhibited tumour growth of AML xenografts in mice, as the tumour weight decreased from 0.618 g (control) to 0.35 g (15 mg/kg) and 0.258 g (30 mg/kg). Suchilactone inhibited Ki-67 expression and increased TUNEL expression in tumour tissue. DISCUSSION AND CONCLUSIONS: Our study is the first to demonstrate suchilactone inhibits AML growth, suggesting that suchilactone is a candidate drug for the treatment of AML. Taylor & Francis 2021-12-28 /pmc/articles/PMC8725822/ /pubmed/34962431 http://dx.doi.org/10.1080/13880209.2021.2017467 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wu, Jingjing
Deng, Yuan
Zhang, Xin
Ma, Jingjing
Zheng, Xinqi
Chen, Yue
Suchilactone inhibits the growth of acute myeloid leukaemia by inactivating SHP2
title Suchilactone inhibits the growth of acute myeloid leukaemia by inactivating SHP2
title_full Suchilactone inhibits the growth of acute myeloid leukaemia by inactivating SHP2
title_fullStr Suchilactone inhibits the growth of acute myeloid leukaemia by inactivating SHP2
title_full_unstemmed Suchilactone inhibits the growth of acute myeloid leukaemia by inactivating SHP2
title_short Suchilactone inhibits the growth of acute myeloid leukaemia by inactivating SHP2
title_sort suchilactone inhibits the growth of acute myeloid leukaemia by inactivating shp2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725822/
https://www.ncbi.nlm.nih.gov/pubmed/34962431
http://dx.doi.org/10.1080/13880209.2021.2017467
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