Novel isobavachalcone derivatives induce apoptosis and necroptosis in human non-small cell lung cancer H1975 cells
AbstractIn this study, seventeen isobavachalcone (IBC) derivatives (1–17) were synthesised, and evaluated for their cytotoxic activity against three human lung cancer cell lines. Among these derivatives, compound 16 displayed the most potent cytotoxic activity against H1975 and A549 cells, with IC50...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2292006 |
| _version_ | 1797382159997075456 |
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| author | Jie Chen Long Zhao Meng-Fan Xu Di Huang Xiao-Long Sun Yu-Xin Zhang Hong-Mei Li Cheng-Zhu Wu |
| author_facet | Jie Chen Long Zhao Meng-Fan Xu Di Huang Xiao-Long Sun Yu-Xin Zhang Hong-Mei Li Cheng-Zhu Wu |
| author_sort | Jie Chen |
| collection | DOAJ |
| description | AbstractIn this study, seventeen isobavachalcone (IBC) derivatives (1–17) were synthesised, and evaluated for their cytotoxic activity against three human lung cancer cell lines. Among these derivatives, compound 16 displayed the most potent cytotoxic activity against H1975 and A549 cells, with IC50 values of 4.35 and 14.21 μM, respectively. Compared with IBC, compound 16 exhibited up to 4.11-fold enhancement of cytotoxic activity on human non-small cell lung cancer H1975 cells. In addition, we found that compound 16 suppressed H1975 cells via inducing apoptosis and necroptosis. The initial mechanism of compound 16 induced cell death in H1975 cells involves the increasing of Bax/Bcl-2 ratio and Cyt C protein level, down-regulating of Akt protein level, and cleaving caspase-9 and -3 induced apoptosis; the up-regulation of RIP3, p-RIP3, MLKL, and p-MLKL levels induced necroptosis. Moreover, compound 16 also caused mitochondrial dysfunction, thereby decreasing cellular ATP levels, and resulting in excessive reactive oxygen species (ROS) accumulation. |
| first_indexed | 2024-03-08T21:01:25Z |
| format | Article |
| id | doaj.art-3c2d2bea8c724991b0b42b3b6d0b9c6f |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-08T21:01:25Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-3c2d2bea8c724991b0b42b3b6d0b9c6f2023-12-22T13:51:54ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2023.2292006Novel isobavachalcone derivatives induce apoptosis and necroptosis in human non-small cell lung cancer H1975 cellsJie Chen0Long Zhao1Meng-Fan Xu2Di Huang3Xiao-Long Sun4Yu-Xin Zhang5Hong-Mei Li6Cheng-Zhu Wu7School of Pharmacy, Bengbu Medical College, Bengbu, Anhui, ChinaSchool of Pharmacy, Bengbu Medical College, Bengbu, Anhui, ChinaSchool of Pharmacy, Bengbu Medical College, Bengbu, Anhui, ChinaSchool of Pharmacy, Bengbu Medical College, Bengbu, Anhui, ChinaSchool of Pharmacy, Bengbu Medical College, Bengbu, Anhui, ChinaAnhui Province Biochemical Pharmaceutical Engineering Technology Research Center, Bengbu, Anhui, ChinaSchool of Pharmacy, Bengbu Medical College, Bengbu, Anhui, ChinaSchool of Pharmacy, Bengbu Medical College, Bengbu, Anhui, ChinaAbstractIn this study, seventeen isobavachalcone (IBC) derivatives (1–17) were synthesised, and evaluated for their cytotoxic activity against three human lung cancer cell lines. Among these derivatives, compound 16 displayed the most potent cytotoxic activity against H1975 and A549 cells, with IC50 values of 4.35 and 14.21 μM, respectively. Compared with IBC, compound 16 exhibited up to 4.11-fold enhancement of cytotoxic activity on human non-small cell lung cancer H1975 cells. In addition, we found that compound 16 suppressed H1975 cells via inducing apoptosis and necroptosis. The initial mechanism of compound 16 induced cell death in H1975 cells involves the increasing of Bax/Bcl-2 ratio and Cyt C protein level, down-regulating of Akt protein level, and cleaving caspase-9 and -3 induced apoptosis; the up-regulation of RIP3, p-RIP3, MLKL, and p-MLKL levels induced necroptosis. Moreover, compound 16 also caused mitochondrial dysfunction, thereby decreasing cellular ATP levels, and resulting in excessive reactive oxygen species (ROS) accumulation.https://www.tandfonline.com/doi/10.1080/14756366.2023.2292006Isobavachalcone derivativesNSCLCapoptosisnecroptosisRIP3 |
| spellingShingle | Jie Chen Long Zhao Meng-Fan Xu Di Huang Xiao-Long Sun Yu-Xin Zhang Hong-Mei Li Cheng-Zhu Wu Novel isobavachalcone derivatives induce apoptosis and necroptosis in human non-small cell lung cancer H1975 cells Journal of Enzyme Inhibition and Medicinal Chemistry Isobavachalcone derivatives NSCLC apoptosis necroptosis RIP3 |
| title | Novel isobavachalcone derivatives induce apoptosis and necroptosis in human non-small cell lung cancer H1975 cells |
| title_full | Novel isobavachalcone derivatives induce apoptosis and necroptosis in human non-small cell lung cancer H1975 cells |
| title_fullStr | Novel isobavachalcone derivatives induce apoptosis and necroptosis in human non-small cell lung cancer H1975 cells |
| title_full_unstemmed | Novel isobavachalcone derivatives induce apoptosis and necroptosis in human non-small cell lung cancer H1975 cells |
| title_short | Novel isobavachalcone derivatives induce apoptosis and necroptosis in human non-small cell lung cancer H1975 cells |
| title_sort | novel isobavachalcone derivatives induce apoptosis and necroptosis in human non small cell lung cancer h1975 cells |
| topic | Isobavachalcone derivatives NSCLC apoptosis necroptosis RIP3 |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2292006 |
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