Sensitization effect of kaempferol from persimmon leaves on HepG2 hepatoma cells with ABT-199 resistance and its molecular mechanisms
ABT-199 (venetoclax) is the first-in-class selective B-cell lymphoma 2 (BCL2) inhibitor, which is known to be ineffective towards liver cancer cells. Here, we investigated the efficacy and the underlying molecular processes of the sensitization effect of kaempferol isolated from persimmon leaves (KP...
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| Format: | Article |
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Frontiers Media
2022
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| Online Access: | http://psasir.upm.edu.my/id/eprint/103172/ |
| _version_ | 1848863952162783232 |
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| author | Chen, Li Jiang, Xudong Gao, Si Liu, Xueping Gao, Ying Siew, Audrey Foong Kow Tham, Chau Ling Ming, Tatt Lee |
| author_facet | Chen, Li Jiang, Xudong Gao, Si Liu, Xueping Gao, Ying Siew, Audrey Foong Kow Tham, Chau Ling Ming, Tatt Lee |
| author_sort | Chen, Li |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | ABT-199 (venetoclax) is the first-in-class selective B-cell lymphoma 2 (BCL2) inhibitor, which is known to be ineffective towards liver cancer cells. Here, we investigated the efficacy and the underlying molecular processes of the sensitization effect of kaempferol isolated from persimmon leaves (KPL) on the ABT-199-resistant HepG2 cells. The effects of various doses of KPL coupled with ABT-199 on the proliferation of HepG2 cells and on the H22 liver tumor-bearing mouse model were examined, as well as the underlying mechanisms. Our findings showed that ABT-199 alone, in contrast to KPL, had no significant impact on hepatoma cell growth, both in vitro and in vivo. Interestingly, the combination therapy showed significantly higher anti-hepatoma efficacy. Mechanistic studies revealed that combining KPL and ABT-199 may promote both early and late apoptosis, as well as decrease the mitochondrial membrane potential in HepG2 cells. Western blot analysis showed that combination of KPL and ABT-199 significantly reduced the expression of the anti-apoptotic proteins Bcl-2, Bcl-xL, and Mcl-1, raised the expression of Bax and cleaved caspase 3, and enhanced cytochrome C release and Bax translocation. Therefore, KPL combined with ABT-199 has a potential application prospect in the treatment of hepatocellular carcinoma. |
| first_indexed | 2025-11-15T13:41:05Z |
| format | Article |
| id | upm-103172 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-15T13:41:05Z |
| publishDate | 2022 |
| publisher | Frontiers Media |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1031722023-12-04T02:48:31Z http://psasir.upm.edu.my/id/eprint/103172/ Sensitization effect of kaempferol from persimmon leaves on HepG2 hepatoma cells with ABT-199 resistance and its molecular mechanisms Chen, Li Jiang, Xudong Gao, Si Liu, Xueping Gao, Ying Siew, Audrey Foong Kow Tham, Chau Ling Ming, Tatt Lee ABT-199 (venetoclax) is the first-in-class selective B-cell lymphoma 2 (BCL2) inhibitor, which is known to be ineffective towards liver cancer cells. Here, we investigated the efficacy and the underlying molecular processes of the sensitization effect of kaempferol isolated from persimmon leaves (KPL) on the ABT-199-resistant HepG2 cells. The effects of various doses of KPL coupled with ABT-199 on the proliferation of HepG2 cells and on the H22 liver tumor-bearing mouse model were examined, as well as the underlying mechanisms. Our findings showed that ABT-199 alone, in contrast to KPL, had no significant impact on hepatoma cell growth, both in vitro and in vivo. Interestingly, the combination therapy showed significantly higher anti-hepatoma efficacy. Mechanistic studies revealed that combining KPL and ABT-199 may promote both early and late apoptosis, as well as decrease the mitochondrial membrane potential in HepG2 cells. Western blot analysis showed that combination of KPL and ABT-199 significantly reduced the expression of the anti-apoptotic proteins Bcl-2, Bcl-xL, and Mcl-1, raised the expression of Bax and cleaved caspase 3, and enhanced cytochrome C release and Bax translocation. Therefore, KPL combined with ABT-199 has a potential application prospect in the treatment of hepatocellular carcinoma. Frontiers Media 2022 Article PeerReviewed Chen, Li and Jiang, Xudong and Gao, Si and Liu, Xueping and Gao, Ying and Siew, Audrey Foong Kow and Tham, Chau Ling and Ming, Tatt Lee (2022) Sensitization effect of kaempferol from persimmon leaves on HepG2 hepatoma cells with ABT-199 resistance and its molecular mechanisms. Frontiers in Pharmacology, 13. art. no. 1032069. pp. 1-15. ISSN 1663-9812 https://www.frontiersin.org/articles/10.3389/fphar.2022.1032069/full 10.3389/fphar.2022.1032069 |
| spellingShingle | Chen, Li Jiang, Xudong Gao, Si Liu, Xueping Gao, Ying Siew, Audrey Foong Kow Tham, Chau Ling Ming, Tatt Lee Sensitization effect of kaempferol from persimmon leaves on HepG2 hepatoma cells with ABT-199 resistance and its molecular mechanisms |
| title | Sensitization effect of kaempferol from persimmon leaves on HepG2 hepatoma cells with ABT-199 resistance and its molecular mechanisms |
| title_full | Sensitization effect of kaempferol from persimmon leaves on HepG2 hepatoma cells with ABT-199 resistance and its molecular mechanisms |
| title_fullStr | Sensitization effect of kaempferol from persimmon leaves on HepG2 hepatoma cells with ABT-199 resistance and its molecular mechanisms |
| title_full_unstemmed | Sensitization effect of kaempferol from persimmon leaves on HepG2 hepatoma cells with ABT-199 resistance and its molecular mechanisms |
| title_short | Sensitization effect of kaempferol from persimmon leaves on HepG2 hepatoma cells with ABT-199 resistance and its molecular mechanisms |
| title_sort | sensitization effect of kaempferol from persimmon leaves on hepg2 hepatoma cells with abt-199 resistance and its molecular mechanisms |
| url | http://psasir.upm.edu.my/id/eprint/103172/ http://psasir.upm.edu.my/id/eprint/103172/ http://psasir.upm.edu.my/id/eprint/103172/ |