Antitumor Effects and the Compatibility Mechanisms of Herb Pair Scleromitrion diffusum (Willd.) R. J. Wang–Sculellaria barbata D. Don

Herb pair Scleromitrion diffusum (Willd.) R. J. Wang (HD) and Scutellaria barbata D. Don (SB) has been most frequently used for cancer treatment in traditional Chinese medicine. This study aimed to explore the in vitro and in vivo antitumor effects of HD-SB extract and to elucidate the underlying co...

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Main Authors: Li Lu, Sheng Zhan, Xiaohui Liu, Xin Zhao, Xiukun Lin, Huanli Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-03-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2020.00292/full
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author Li Lu
Sheng Zhan
Xiaohui Liu
Xin Zhao
Xiukun Lin
Huanli Xu
author_facet Li Lu
Sheng Zhan
Xiaohui Liu
Xin Zhao
Xiukun Lin
Huanli Xu
author_sort Li Lu
collection DOAJ
description Herb pair Scleromitrion diffusum (Willd.) R. J. Wang (HD) and Scutellaria barbata D. Don (SB) has been most frequently used for cancer treatment in traditional Chinese medicine. This study aimed to explore the in vitro and in vivo antitumor effects of HD-SB extract and to elucidate the underlying compatibility mechanisms. HD, SB, and HD-SB extracts were prepared, and the components were detected by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method. The in vitro antitumor effects of various concentrations of these extract were detected on several tumor cell lines using MTS assay. The in vivo antitumor effects were evaluated in Panc28 cells–bearing nude mice model. The compatibility mechanisms of herb pair HD-SB were evaluated based on the systems pharmacology strategy and then validated by cellular experiments. HD-SB extract was demonstrated to inhibit the proliferation of the cancer cell lines dose dependently by MTS assay. In vivo antitumor effects of HD-SB were much more potent than either of the two single herbs in Panc28 xenograft mice model. A total 29 active ingredients involved in antitumor effects were selected from HD and SB, and the “herb–composition–target–disease” network was constructed. Then, 58 cancer-related targets and 66 KEGG pathways were identified, and PTGS2-, HSP90-, EGFR-, MMP2-, PPARγ-, and GSTP-mediated pathways were predicted to be the antitumor mechanisms of HD-SB. The cellular experiments showed that HD-SB significantly induced cancer cell apoptosis, decreased p-EGFR, HSP90 and bcl-2 expressions, and increased PPARγ, bax, cleaved caspase 3, cleaved PARP, p-AKT, and p-PI3K expressions compared with HD or SB treatment. Our study showed that HD-SB inhibited tumor growth both in vitro and in vivo, which might be related with apoptosis induction via the EGFR/PPARγ/PI3K/AKT pathway.
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spelling doaj.art-90a07a9a024b460a880c28c8aa56b01a2022-12-21T23:54:53ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-03-011110.3389/fphar.2020.00292500944Antitumor Effects and the Compatibility Mechanisms of Herb Pair Scleromitrion diffusum (Willd.) R. J. Wang–Sculellaria barbata D. DonLi Lu0Sheng Zhan1Xiaohui Liu2Xin Zhao3Xiukun Lin4Huanli Xu5Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaDepartment of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaDepartment of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaThe Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, ChinaDepartment of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaDepartment of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaHerb pair Scleromitrion diffusum (Willd.) R. J. Wang (HD) and Scutellaria barbata D. Don (SB) has been most frequently used for cancer treatment in traditional Chinese medicine. This study aimed to explore the in vitro and in vivo antitumor effects of HD-SB extract and to elucidate the underlying compatibility mechanisms. HD, SB, and HD-SB extracts were prepared, and the components were detected by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method. The in vitro antitumor effects of various concentrations of these extract were detected on several tumor cell lines using MTS assay. The in vivo antitumor effects were evaluated in Panc28 cells–bearing nude mice model. The compatibility mechanisms of herb pair HD-SB were evaluated based on the systems pharmacology strategy and then validated by cellular experiments. HD-SB extract was demonstrated to inhibit the proliferation of the cancer cell lines dose dependently by MTS assay. In vivo antitumor effects of HD-SB were much more potent than either of the two single herbs in Panc28 xenograft mice model. A total 29 active ingredients involved in antitumor effects were selected from HD and SB, and the “herb–composition–target–disease” network was constructed. Then, 58 cancer-related targets and 66 KEGG pathways were identified, and PTGS2-, HSP90-, EGFR-, MMP2-, PPARγ-, and GSTP-mediated pathways were predicted to be the antitumor mechanisms of HD-SB. The cellular experiments showed that HD-SB significantly induced cancer cell apoptosis, decreased p-EGFR, HSP90 and bcl-2 expressions, and increased PPARγ, bax, cleaved caspase 3, cleaved PARP, p-AKT, and p-PI3K expressions compared with HD or SB treatment. Our study showed that HD-SB inhibited tumor growth both in vitro and in vivo, which might be related with apoptosis induction via the EGFR/PPARγ/PI3K/AKT pathway.https://www.frontiersin.org/article/10.3389/fphar.2020.00292/fullScleromitrion diffusum (Willd.) R. J. Wang (HD)Scutellaria barbata D. Don (SB)network pharmacologyantitumorapoptosis
spellingShingle Li Lu
Sheng Zhan
Xiaohui Liu
Xin Zhao
Xiukun Lin
Huanli Xu
Antitumor Effects and the Compatibility Mechanisms of Herb Pair Scleromitrion diffusum (Willd.) R. J. Wang–Sculellaria barbata D. Don
Frontiers in Pharmacology
Scleromitrion diffusum (Willd.) R. J. Wang (HD)
Scutellaria barbata D. Don (SB)
network pharmacology
antitumor
apoptosis
title Antitumor Effects and the Compatibility Mechanisms of Herb Pair Scleromitrion diffusum (Willd.) R. J. Wang–Sculellaria barbata D. Don
title_full Antitumor Effects and the Compatibility Mechanisms of Herb Pair Scleromitrion diffusum (Willd.) R. J. Wang–Sculellaria barbata D. Don
title_fullStr Antitumor Effects and the Compatibility Mechanisms of Herb Pair Scleromitrion diffusum (Willd.) R. J. Wang–Sculellaria barbata D. Don
title_full_unstemmed Antitumor Effects and the Compatibility Mechanisms of Herb Pair Scleromitrion diffusum (Willd.) R. J. Wang–Sculellaria barbata D. Don
title_short Antitumor Effects and the Compatibility Mechanisms of Herb Pair Scleromitrion diffusum (Willd.) R. J. Wang–Sculellaria barbata D. Don
title_sort antitumor effects and the compatibility mechanisms of herb pair scleromitrion diffusum willd r j wang sculellaria barbata d don
topic Scleromitrion diffusum (Willd.) R. J. Wang (HD)
Scutellaria barbata D. Don (SB)
network pharmacology
antitumor
apoptosis
url https://www.frontiersin.org/article/10.3389/fphar.2020.00292/full
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