Isoquercitrin Suppresses Esophageal Squamous Cell Carcinoma (ESCC) by Inducing Excessive Autophagy and Promoting Apoptosis via the AKT/mTOR Signaling Pathway
Esophageal squamous cell carcinoma (ESCC), one of the most frequent malignant tumors of the digestive system, is marked by a poor prognosis and high mortality rate. There is a critical need for effective therapeutic strategies with minimal side effects. Isoquercitrin (IQ) is a natural compound with...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/14/6/694 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849435380199194624 |
|---|---|
| author | Zhibin Liu Ke Huang Hai Huang Eungyung Kim Hyeonjin Kim Chae Yeon Kim Dong Joon Kim Sang In Lee Sangsik Kim Do Yoon Kim Kangdong Liu Zae Young Ryoo Mee-Hyun Lee Lei Ma Myoung Ok Kim |
| author_facet | Zhibin Liu Ke Huang Hai Huang Eungyung Kim Hyeonjin Kim Chae Yeon Kim Dong Joon Kim Sang In Lee Sangsik Kim Do Yoon Kim Kangdong Liu Zae Young Ryoo Mee-Hyun Lee Lei Ma Myoung Ok Kim |
| author_sort | Zhibin Liu |
| collection | DOAJ |
| description | Esophageal squamous cell carcinoma (ESCC), one of the most frequent malignant tumors of the digestive system, is marked by a poor prognosis and high mortality rate. There is a critical need for effective therapeutic strategies with minimal side effects. Isoquercitrin (IQ) is a natural compound with potent antioxidant properties in cancer and cardiovascular diseases. However, its specific effects and mechanisms in ESCC remain largely unexplored. This study aims to investigate the effects of IQ in ESCC cells and elucidate the mechanisms underlying its therapeutic effects. Specifically, its impact on cell proliferation, colony formation, migration, and invasion was assessed using cell viability assay, morphology, transwell, and colony formation assays. The effects on apoptosis were evaluated by flow cytometry, while immunofluorescence (IF) staining and Western blotting were performed to confirm the underlying mechanisms. The in vivo anti-cancer effects of IQ were then evaluated using a xenograft tumor model. Our results demonstrate that IQ inhibits ESCC cell growth and colony formation while promoting its apoptosis by enhancing caspase activation and downregulating Bcl-2 expression. Furthermore, IQ suppresses cell migration by modulating the epithelial–mesenchymal transition-related proteins. Additionally, IQ induces excessive autophagy by promoting reactive oxygen species accumulation and inhibiting the AKT/mTOR signaling pathway. Importantly, IQ effectively reduces tumor growth in vivo, highlighting its potential as a therapeutic agent for ESCC. |
| format | Article |
| id | doaj-art-1f0b637a250b4e5e987479643d2a2d2c |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-1f0b637a250b4e5e987479643d2a2d2c2025-08-20T03:26:20ZengMDPI AGAntioxidants2076-39212025-06-0114669410.3390/antiox14060694Isoquercitrin Suppresses Esophageal Squamous Cell Carcinoma (ESCC) by Inducing Excessive Autophagy and Promoting Apoptosis via the AKT/mTOR Signaling PathwayZhibin Liu0Ke Huang1Hai Huang2Eungyung Kim3Hyeonjin Kim4Chae Yeon Kim5Dong Joon Kim6Sang In Lee7Sangsik Kim8Do Yoon Kim9Kangdong Liu10Zae Young Ryoo11Mee-Hyun Lee12Lei Ma13Myoung Ok Kim14Department of Animal Science and Biotechnology, Research Institute for Innovative Animal Science, Kyungpook National University, Sangju-si 37224, Gyeongsang buk-do, Republic of KoreaDepartment of Animal Science and Biotechnology, Research Institute for Innovative Animal Science, Kyungpook National University, Sangju-si 37224, Gyeongsang buk-do, Republic of KoreaHenan International Joint Laboratory of TCM Syndrome and Prescription in Signaling, Traditional Chinese Medicine (Zhong Jing) School, Henan University of Chinese Medicine, Zhengzhou 450046, ChinaDepartment of Oral and Maxillofacial Surgery, School of Dentistry, University of Texas Health Science Cente at San Antonio, San Antonio, TX 78229, USADepartment of Animal Science and Biotechnology, Research Institute for Innovative Animal Science, Kyungpook National University, Sangju-si 37224, Gyeongsang buk-do, Republic of KoreaDepartment of Animal Science and Biotechnology, Research Institute for Innovative Animal Science, Kyungpook National University, Sangju-si 37224, Gyeongsang buk-do, Republic of KoreaDepartment of Microbiology, College of Medicine, Dankook University, Cheonan 31116, Chungcheongnam-do, Republic of KoreaDepartment of Animal Science and Biotechnology, Research Institute for Innovative Animal Science, Kyungpook National University, Sangju-si 37224, Gyeongsang buk-do, Republic of KoreaDepartment of Energy Chemical Engineering, Kyungpook National University, Sangju-si 37224, Gyeongsang buk-do, Republic of KoreaGyeongsangbukdo Livestock Research Institute, Yeongju 36052, Gyeongsang buk-do, Republic of KoreaChina–US (Henan) Hormel Cancer Institute, Zhengzhou 450008, ChinaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Gyeongsang buk-do, Republic of KoreaKorean Medicine Research Center for Bi-Wi Control Based Gut-Brain System Regulation, College of Korean Medicine, Dongshin University, Naju-si 58245, Jeollanam-do, Republic of KoreaDepartment of Animal Science and Biotechnology, Research Institute for Innovative Animal Science, Kyungpook National University, Sangju-si 37224, Gyeongsang buk-do, Republic of KoreaDepartment of Animal Science and Biotechnology, Research Institute for Innovative Animal Science, Kyungpook National University, Sangju-si 37224, Gyeongsang buk-do, Republic of KoreaEsophageal squamous cell carcinoma (ESCC), one of the most frequent malignant tumors of the digestive system, is marked by a poor prognosis and high mortality rate. There is a critical need for effective therapeutic strategies with minimal side effects. Isoquercitrin (IQ) is a natural compound with potent antioxidant properties in cancer and cardiovascular diseases. However, its specific effects and mechanisms in ESCC remain largely unexplored. This study aims to investigate the effects of IQ in ESCC cells and elucidate the mechanisms underlying its therapeutic effects. Specifically, its impact on cell proliferation, colony formation, migration, and invasion was assessed using cell viability assay, morphology, transwell, and colony formation assays. The effects on apoptosis were evaluated by flow cytometry, while immunofluorescence (IF) staining and Western blotting were performed to confirm the underlying mechanisms. The in vivo anti-cancer effects of IQ were then evaluated using a xenograft tumor model. Our results demonstrate that IQ inhibits ESCC cell growth and colony formation while promoting its apoptosis by enhancing caspase activation and downregulating Bcl-2 expression. Furthermore, IQ suppresses cell migration by modulating the epithelial–mesenchymal transition-related proteins. Additionally, IQ induces excessive autophagy by promoting reactive oxygen species accumulation and inhibiting the AKT/mTOR signaling pathway. Importantly, IQ effectively reduces tumor growth in vivo, highlighting its potential as a therapeutic agent for ESCC.https://www.mdpi.com/2076-3921/14/6/694esophageal squamous cell carcinomaAKT/mTORanti-cancerexcessive autophagyapoptosis |
| spellingShingle | Zhibin Liu Ke Huang Hai Huang Eungyung Kim Hyeonjin Kim Chae Yeon Kim Dong Joon Kim Sang In Lee Sangsik Kim Do Yoon Kim Kangdong Liu Zae Young Ryoo Mee-Hyun Lee Lei Ma Myoung Ok Kim Isoquercitrin Suppresses Esophageal Squamous Cell Carcinoma (ESCC) by Inducing Excessive Autophagy and Promoting Apoptosis via the AKT/mTOR Signaling Pathway Antioxidants esophageal squamous cell carcinoma AKT/mTOR anti-cancer excessive autophagy apoptosis |
| title | Isoquercitrin Suppresses Esophageal Squamous Cell Carcinoma (ESCC) by Inducing Excessive Autophagy and Promoting Apoptosis via the AKT/mTOR Signaling Pathway |
| title_full | Isoquercitrin Suppresses Esophageal Squamous Cell Carcinoma (ESCC) by Inducing Excessive Autophagy and Promoting Apoptosis via the AKT/mTOR Signaling Pathway |
| title_fullStr | Isoquercitrin Suppresses Esophageal Squamous Cell Carcinoma (ESCC) by Inducing Excessive Autophagy and Promoting Apoptosis via the AKT/mTOR Signaling Pathway |
| title_full_unstemmed | Isoquercitrin Suppresses Esophageal Squamous Cell Carcinoma (ESCC) by Inducing Excessive Autophagy and Promoting Apoptosis via the AKT/mTOR Signaling Pathway |
| title_short | Isoquercitrin Suppresses Esophageal Squamous Cell Carcinoma (ESCC) by Inducing Excessive Autophagy and Promoting Apoptosis via the AKT/mTOR Signaling Pathway |
| title_sort | isoquercitrin suppresses esophageal squamous cell carcinoma escc by inducing excessive autophagy and promoting apoptosis via the akt mtor signaling pathway |
| topic | esophageal squamous cell carcinoma AKT/mTOR anti-cancer excessive autophagy apoptosis |
| url | https://www.mdpi.com/2076-3921/14/6/694 |
| work_keys_str_mv | AT zhibinliu isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT kehuang isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT haihuang isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT eungyungkim isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT hyeonjinkim isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT chaeyeonkim isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT dongjoonkim isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT sanginlee isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT sangsikkim isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT doyoonkim isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT kangdongliu isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT zaeyoungryoo isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT meehyunlee isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT leima isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway AT myoungokkim isoquercitrinsuppressesesophagealsquamouscellcarcinomaesccbyinducingexcessiveautophagyandpromotingapoptosisviatheaktmtorsignalingpathway |