Ajuforrestin A, an Abietane Diterpenoid from <i>Ajuga ovalifolia</i> var. <i>calanthe</i>, Induces A549 Cell Apoptosis by Targeting SHP2
The Src-homology 2 domain-containing phosphatase 2 (SHP2), which is encoded by PTPN11, participates in many cellular signaling pathways and is closely related to various tumorigenesis. Inhibition of the abnormal activity of SHP2 by small molecules is an important part of cancer treatment. Here, thre...
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MDPI AG
2022-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/17/5469 |
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| author | Hongling Yan Miao Jiang Fujin Yang Xueyong Tang Mao Lin Chunyan Zhou Yuzhu Tan Deming Liu |
| author_facet | Hongling Yan Miao Jiang Fujin Yang Xueyong Tang Mao Lin Chunyan Zhou Yuzhu Tan Deming Liu |
| author_sort | Hongling Yan |
| collection | DOAJ |
| description | The Src-homology 2 domain-containing phosphatase 2 (SHP2), which is encoded by PTPN11, participates in many cellular signaling pathways and is closely related to various tumorigenesis. Inhibition of the abnormal activity of SHP2 by small molecules is an important part of cancer treatment. Here, three abietane diterpenoids, named compounds <b>1</b>–<b>3</b>, were isolated from <i>Ajuga ovalifolia</i> var. <i>calantha</i>. Spectroscopic analysis was used to identify the exact structure of the compounds. The enzymatic kinetic experiment and the cellular thermal shift assay showed compound <b>2</b> selectively inhibited SHP2 activity in vitro. Molecular docking indicated compound <b>2</b> targeted the SHP2 catalytic domain. The predicted pharmacokinetic properties by SwissADME revealed that compound <b>2</b> passed the majority of the parameters of common drug discovery rules. Compound <b>2</b> restrained A549 proliferation (IC<sub>50</sub> = 8.68 ± 0.96 μM), invasion and caused A549 cell apoptosis by inhibiting the SHP2–ERK/AKT signaling pathway. Finally, compound <b>2</b> (Ajuforrestin A) is a potent and efficacious SHP2 inhibitor and may be a promising compound for human lung epithelial cancer treatment. |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T01:30:35Z |
| publishDate | 2022-08-01 |
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| spelling | doaj.art-5bf07036e3ec473d8c06e2ca248d37e12023-11-23T13:42:31ZengMDPI AGMolecules1420-30492022-08-012717546910.3390/molecules27175469Ajuforrestin A, an Abietane Diterpenoid from <i>Ajuga ovalifolia</i> var. <i>calanthe</i>, Induces A549 Cell Apoptosis by Targeting SHP2Hongling Yan0Miao Jiang1Fujin Yang2Xueyong Tang3Mao Lin4Chunyan Zhou5Yuzhu Tan6Deming Liu7Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaKey Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaChongqing Clinical Research Center for Dermatology, Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400011, ChinaChongqing Clinical Research Center for Dermatology, Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400011, ChinaChongqing Clinical Research Center for Dermatology, Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400011, ChinaGeneral Surgery, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, ChinaKey Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaChongqing Clinical Research Center for Dermatology, Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400011, ChinaThe Src-homology 2 domain-containing phosphatase 2 (SHP2), which is encoded by PTPN11, participates in many cellular signaling pathways and is closely related to various tumorigenesis. Inhibition of the abnormal activity of SHP2 by small molecules is an important part of cancer treatment. Here, three abietane diterpenoids, named compounds <b>1</b>–<b>3</b>, were isolated from <i>Ajuga ovalifolia</i> var. <i>calantha</i>. Spectroscopic analysis was used to identify the exact structure of the compounds. The enzymatic kinetic experiment and the cellular thermal shift assay showed compound <b>2</b> selectively inhibited SHP2 activity in vitro. Molecular docking indicated compound <b>2</b> targeted the SHP2 catalytic domain. The predicted pharmacokinetic properties by SwissADME revealed that compound <b>2</b> passed the majority of the parameters of common drug discovery rules. Compound <b>2</b> restrained A549 proliferation (IC<sub>50</sub> = 8.68 ± 0.96 μM), invasion and caused A549 cell apoptosis by inhibiting the SHP2–ERK/AKT signaling pathway. Finally, compound <b>2</b> (Ajuforrestin A) is a potent and efficacious SHP2 inhibitor and may be a promising compound for human lung epithelial cancer treatment.https://www.mdpi.com/1420-3049/27/17/5469SHP2Ajuforrestin A<i>Ajuga ovalifolia</i> var. <i>calantha</i>apoptosisERK/AKT pathway |
| spellingShingle | Hongling Yan Miao Jiang Fujin Yang Xueyong Tang Mao Lin Chunyan Zhou Yuzhu Tan Deming Liu Ajuforrestin A, an Abietane Diterpenoid from <i>Ajuga ovalifolia</i> var. <i>calanthe</i>, Induces A549 Cell Apoptosis by Targeting SHP2 Molecules SHP2 Ajuforrestin A <i>Ajuga ovalifolia</i> var. <i>calantha</i> apoptosis ERK/AKT pathway |
| title | Ajuforrestin A, an Abietane Diterpenoid from <i>Ajuga ovalifolia</i> var. <i>calanthe</i>, Induces A549 Cell Apoptosis by Targeting SHP2 |
| title_full | Ajuforrestin A, an Abietane Diterpenoid from <i>Ajuga ovalifolia</i> var. <i>calanthe</i>, Induces A549 Cell Apoptosis by Targeting SHP2 |
| title_fullStr | Ajuforrestin A, an Abietane Diterpenoid from <i>Ajuga ovalifolia</i> var. <i>calanthe</i>, Induces A549 Cell Apoptosis by Targeting SHP2 |
| title_full_unstemmed | Ajuforrestin A, an Abietane Diterpenoid from <i>Ajuga ovalifolia</i> var. <i>calanthe</i>, Induces A549 Cell Apoptosis by Targeting SHP2 |
| title_short | Ajuforrestin A, an Abietane Diterpenoid from <i>Ajuga ovalifolia</i> var. <i>calanthe</i>, Induces A549 Cell Apoptosis by Targeting SHP2 |
| title_sort | ajuforrestin a an abietane diterpenoid from i ajuga ovalifolia i var i calanthe i induces a549 cell apoptosis by targeting shp2 |
| topic | SHP2 Ajuforrestin A <i>Ajuga ovalifolia</i> var. <i>calantha</i> apoptosis ERK/AKT pathway |
| url | https://www.mdpi.com/1420-3049/27/17/5469 |
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