Icaritin Represses Autophagy to Promote Colorectal Cancer Cell Apoptosis and Sensitized Low‐Temperature Photothermal Therapy via Targeting HSP90‐TXNDC9 Interactions
Abstract Colorectal cancer (CRC) ranks among the leading causes of cancer‐related dea ths worldwide, and the rising incidence and mortality of CRC underscores the urgent need for better understanding and management strategies. Icaritin (ICA) is the metabolites of icariin, a natural flavonoid glycosi...
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202412953 |
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| author | Dan He Siliang Chen Xiaoyun Wang Xiang Wen Changyang Gong Lei Liu Gu He |
| author_facet | Dan He Siliang Chen Xiaoyun Wang Xiang Wen Changyang Gong Lei Liu Gu He |
| author_sort | Dan He |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) ranks among the leading causes of cancer‐related dea ths worldwide, and the rising incidence and mortality of CRC underscores the urgent need for better understanding and management strategies. Icaritin (ICA) is the metabolites of icariin, a natural flavonoid glycoside compound derived from the stems and leaves of Epimedium. It has broad spectrum antitumor activity and inhibits the proliferation, migration, and invasion of CRC cells, and causes S phase cell cycle arrest. It exerts its antitumor effects against CRC through repressing autophagy to promote CRC cell apoptosis via interfering the HSP90‐TXNDC9 interactions. The safety and efficacy of ICA are also affirmed in a mouse xenograft model. Additionally, to test whether ICA exerts synergistic effects with low‐temperature photothermal therapy (LTPTT), a novel nanodrug delivery system, employing SiO2 nanocarriers, is designed aiming to load ICA with photothermal materials polydopamine (PDA), and folic acid (FA). This SiO2/Ica‐PDA‐FA multifunctional nanocomposite actively targets tumor tissues through the high affinity of FA for cancer cells. Once internalized, the acidic intracellular environment triggers the controlled release of ICA, inhibiting HSP90‐TXNDC9 interactions. By LTPTT and ICA drug therapy under near‐infrared illumination, a dual synergistic antitumor effect is achieved, holding promise for enhancing therapeutic outcomes in CRC treatment. |
| format | Article |
| id | doaj-art-159ab194ff02482d8108a16fce4e1480 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-159ab194ff02482d8108a16fce4e14802025-08-20T02:02:16ZengWileyAdvanced Science2198-38442025-05-011220n/an/a10.1002/advs.202412953Icaritin Represses Autophagy to Promote Colorectal Cancer Cell Apoptosis and Sensitized Low‐Temperature Photothermal Therapy via Targeting HSP90‐TXNDC9 InteractionsDan He0Siliang Chen1Xiaoyun Wang2Xiang Wen3Changyang Gong4Lei Liu5Gu He6Division of Head & Neck Tumor Multimodality Treatment Cancer Center and Department of Dermatology & Venerology West China Hospital Sichuan University Chengdu 610041 ChinaDivision of Head & Neck Tumor Multimodality Treatment Cancer Center and Department of Dermatology & Venerology West China Hospital Sichuan University Chengdu 610041 ChinaDivision of Head & Neck Tumor Multimodality Treatment Cancer Center and Department of Dermatology & Venerology West China Hospital Sichuan University Chengdu 610041 ChinaDivision of Head & Neck Tumor Multimodality Treatment Cancer Center and Department of Dermatology & Venerology West China Hospital Sichuan University Chengdu 610041 ChinaDivision of Head & Neck Tumor Multimodality Treatment Cancer Center and Department of Dermatology & Venerology West China Hospital Sichuan University Chengdu 610041 ChinaDivision of Head & Neck Tumor Multimodality Treatment Cancer Center and Department of Dermatology & Venerology West China Hospital Sichuan University Chengdu 610041 ChinaLaboratory of Dermatology Clinical Institute of Inflammation and Immunology Frontiers Science Center for Disease‐Related Molecular Network State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaAbstract Colorectal cancer (CRC) ranks among the leading causes of cancer‐related dea ths worldwide, and the rising incidence and mortality of CRC underscores the urgent need for better understanding and management strategies. Icaritin (ICA) is the metabolites of icariin, a natural flavonoid glycoside compound derived from the stems and leaves of Epimedium. It has broad spectrum antitumor activity and inhibits the proliferation, migration, and invasion of CRC cells, and causes S phase cell cycle arrest. It exerts its antitumor effects against CRC through repressing autophagy to promote CRC cell apoptosis via interfering the HSP90‐TXNDC9 interactions. The safety and efficacy of ICA are also affirmed in a mouse xenograft model. Additionally, to test whether ICA exerts synergistic effects with low‐temperature photothermal therapy (LTPTT), a novel nanodrug delivery system, employing SiO2 nanocarriers, is designed aiming to load ICA with photothermal materials polydopamine (PDA), and folic acid (FA). This SiO2/Ica‐PDA‐FA multifunctional nanocomposite actively targets tumor tissues through the high affinity of FA for cancer cells. Once internalized, the acidic intracellular environment triggers the controlled release of ICA, inhibiting HSP90‐TXNDC9 interactions. By LTPTT and ICA drug therapy under near‐infrared illumination, a dual synergistic antitumor effect is achieved, holding promise for enhancing therapeutic outcomes in CRC treatment.https://doi.org/10.1002/advs.202412953autophagycolorectal cancericaritinphotothermal therapyHSP90 |
| spellingShingle | Dan He Siliang Chen Xiaoyun Wang Xiang Wen Changyang Gong Lei Liu Gu He Icaritin Represses Autophagy to Promote Colorectal Cancer Cell Apoptosis and Sensitized Low‐Temperature Photothermal Therapy via Targeting HSP90‐TXNDC9 Interactions Advanced Science autophagy colorectal cancer icaritin photothermal therapy HSP90 |
| title | Icaritin Represses Autophagy to Promote Colorectal Cancer Cell Apoptosis and Sensitized Low‐Temperature Photothermal Therapy via Targeting HSP90‐TXNDC9 Interactions |
| title_full | Icaritin Represses Autophagy to Promote Colorectal Cancer Cell Apoptosis and Sensitized Low‐Temperature Photothermal Therapy via Targeting HSP90‐TXNDC9 Interactions |
| title_fullStr | Icaritin Represses Autophagy to Promote Colorectal Cancer Cell Apoptosis and Sensitized Low‐Temperature Photothermal Therapy via Targeting HSP90‐TXNDC9 Interactions |
| title_full_unstemmed | Icaritin Represses Autophagy to Promote Colorectal Cancer Cell Apoptosis and Sensitized Low‐Temperature Photothermal Therapy via Targeting HSP90‐TXNDC9 Interactions |
| title_short | Icaritin Represses Autophagy to Promote Colorectal Cancer Cell Apoptosis and Sensitized Low‐Temperature Photothermal Therapy via Targeting HSP90‐TXNDC9 Interactions |
| title_sort | icaritin represses autophagy to promote colorectal cancer cell apoptosis and sensitized low temperature photothermal therapy via targeting hsp90 txndc9 interactions |
| topic | autophagy colorectal cancer icaritin photothermal therapy HSP90 |
| url | https://doi.org/10.1002/advs.202412953 |
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