Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti‐triple‐negative breast cancer efficacy in vitro and in vivo
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| Format: | Artículo Open Access |
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Wiley
2024
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| author | Ya‐li Ren Jie‐ting Lei Ting‐rui Zhang Peng Lu Dan‐dan Cui Bo Yang Gui‐ying Zhao Fu Peng Zhi‐xing Cao Cheng Peng Yu‐zhi Li |
| author_facet | Ya‐li Ren Jie‐ting Lei Ting‐rui Zhang Peng Lu Dan‐dan Cui Bo Yang Gui‐ying Zhao Fu Peng Zhi‐xing Cao Cheng Peng Yu‐zhi Li Ya‐li Ren Jie‐ting Lei Ting‐rui Zhang Peng Lu Dan‐dan Cui Bo Yang Gui‐ying Zhao Fu Peng Zhi‐xing Cao Cheng Peng Yu‐zhi Li |
| collection | Wiley Open Access |
| contents | Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti‐triple‐negative breast cancer efficacy in vitro and in vivo Ya‐li Ren Jie‐ting Lei Ting‐rui Zhang Peng Lu Dan‐dan Cui Bo Yang Gui‐ying Zhao Fu Peng Zhi‐xing Cao Cheng Peng Yu‐zhi Li Phytotherapy Research AbstractTriple‐negative breast cancer (TNBC) is the most aggressive and lethal clinical subtype and lacks effective targeted therapies at present. Isobavachalcone (IBC), the main active component of Psoralea corylifolia L., has potential anticancer effects. Herein, we identified IBC as a natural sirtuin 2 (SIRT2) inhibitor and characterized the potential mechanisms underlying the inhibition of TNBC. Molecular dynamics analysis, enzyme activity assay, and cellular thermal shift assay were performed to evaluate the combination of IBC and SIRT2. The therapeutic effects, mechanism, and safety of IBC were analyzed in vitro and in vivo using cellular and xenograft models. IBC effectively inhibited SIRT2 enzyme activity with an IC50 value of 0.84 ± 0.22 μM by forming hydrogen bonds with VAL233 and ALA135 within its catalytic domain. In the cellular environment, IBC bound to and stabilized SIRT2, consequently inhibiting cellular proliferation and migration, and inducing apoptosis and cell cycle arrest by disrupting the SIRT2/α‐tubulin interaction and inhibiting the downstream Snail/MMP and STAT3/c‐Myc pathways. In the in vivo model, 30 mg/kg IBC markedly inhibited tumor growth by targeting the SIRT2/α‐tubulin interaction. Furthermore, IBC exerted its effects by inducing apoptosis in tumor tissues and was well‐tolerated. IBC alleviated TNBC by targeting SIRT2 and triggering the reactive oxygen species ROS/β‐catenin/CDK2 axis. It is a promising natural lead compound for future development of SIRT2‐targeting drugs. 10.1002/ptr.8143 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/ptr.8143 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_ptr_8143 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti‐triple‐negative breast cancer efficacy in vitro and in vivo Ya‐li Ren Jie‐ting Lei Ting‐rui Zhang Peng Lu Dan‐dan Cui Bo Yang Gui‐ying Zhao Fu Peng Zhi‐xing Cao Cheng Peng Yu‐zhi Li Phytotherapy Research Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti‐triple‐negative breast cancer efficacy in vitro and in vivo Ya‐li Ren Jie‐ting Lei Ting‐rui Zhang Peng Lu Dan‐dan Cui Bo Yang Gui‐ying Zhao Fu Peng Zhi‐xing Cao Cheng Peng Yu‐zhi Li Phytotherapy Research AbstractTriple‐negative breast cancer (TNBC) is the most aggressive and lethal clinical subtype and lacks effective targeted therapies at present. Isobavachalcone (IBC), the main active component of Psoralea corylifolia L., has potential anticancer effects. Herein, we identified IBC as a natural sirtuin 2 (SIRT2) inhibitor and characterized the potential mechanisms underlying the inhibition of TNBC. Molecular dynamics analysis, enzyme activity assay, and cellular thermal shift assay were performed to evaluate the combination of IBC and SIRT2. The therapeutic effects, mechanism, and safety of IBC were analyzed in vitro and in vivo using cellular and xenograft models. IBC effectively inhibited SIRT2 enzyme activity with an IC50 value of 0.84 ± 0.22 μM by forming hydrogen bonds with VAL233 and ALA135 within its catalytic domain. In the cellular environment, IBC bound to and stabilized SIRT2, consequently inhibiting cellular proliferation and migration, and inducing apoptosis and cell cycle arrest by disrupting the SIRT2/α‐tubulin interaction and inhibiting the downstream Snail/MMP and STAT3/c‐Myc pathways. In the in vivo model, 30 mg/kg IBC markedly inhibited tumor growth by targeting the SIRT2/α‐tubulin interaction. Furthermore, IBC exerted its effects by inducing apoptosis in tumor tissues and was well‐tolerated. IBC alleviated TNBC by targeting SIRT2 and triggering the reactive oxygen species ROS/β‐catenin/CDK2 axis. It is a promising natural lead compound for future development of SIRT2‐targeting drugs. 10.1002/ptr.8143 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti‐triple‐negative breast cancer efficacy in vitro and in vivo |
| topic | Phytotherapy Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/ptr.8143 |