Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma Cells
Hinokitiol is a tropolone-related compound found in heartwood cupressaceous plants. Hinokitiol slows the growth of a variety of cancers through inhibition of cell proliferation. The low water solubility of hinokitiol leads to less bioavailability. This has been highlighted as a major limiting factor...
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MDPI AG
2016-04-01
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| Online Access: | http://www.mdpi.com/1996-1944/9/5/306 |
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| author | Yu-Fang Shen Chia-Che Ho Ming-You Shie Kan Wang Hsin-Yuan Fang |
| author_facet | Yu-Fang Shen Chia-Che Ho Ming-You Shie Kan Wang Hsin-Yuan Fang |
| author_sort | Yu-Fang Shen |
| collection | DOAJ |
| description | Hinokitiol is a tropolone-related compound found in heartwood cupressaceous plants. Hinokitiol slows the growth of a variety of cancers through inhibition of cell proliferation. The low water solubility of hinokitiol leads to less bioavailability. This has been highlighted as a major limiting factor. In this study, mesoporous calcium silicate (MCS) nanoparticles, both pure and hinokitiol-loaded, were synthesized and their effects on A549 cells were analyzed. The results indicate that Hino-MCS nanoparticles induce apoptosis in higher concentration loads (>12.5 μg/mL) for A549 cells. Hino-MCS nanoparticles suppress gene and protein expression levels of multiple drug resistance protein 1 (MDR1). In addition, both the activity and the expression levels of caspase-3/-9 were measured in Hino-MCS nanoparticle-treated A549 cells. The Hino-MCS nanoparticles-triggered apoptosis was blocked by inhibitors of pan-caspase, caspase-3/-9, and antioxidant agents (N-acetylcysteine; NAC). The Hino-MCS nanoparticles enhance reactive oxygen species production and the protein expression levels of caspase-3/-9. Our data suggest that Hino-MCS nanoparticles trigger an intrinsic apoptotic pathway through regulating the function of MDR1 and the production of reactive oxygen species in A549 cells. Therefore, we believe that Hino-MCS nanoparticles may be efficacious in the treatment of drug-resistant human lung cancer in the future. |
| first_indexed | 2024-04-13T14:50:59Z |
| format | Article |
| id | doaj.art-c53640646d634086a6d90d4f31948a57 |
| institution | Directory Open Access Journal |
| issn | 1996-1944 |
| language | English |
| last_indexed | 2024-04-13T14:50:59Z |
| publishDate | 2016-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Materials |
| spelling | doaj.art-c53640646d634086a6d90d4f31948a572022-12-22T02:42:35ZengMDPI AGMaterials1996-19442016-04-019530610.3390/ma9050306ma9050306Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma CellsYu-Fang Shen0Chia-Che Ho1Ming-You Shie2Kan Wang3Hsin-Yuan Fang43D Printing Medical Research Center, China Medical University Hospital, Taichung City 40447, Taiwan3D Printing Medical Research Center, China Medical University Hospital, Taichung City 40447, Taiwan3D Printing Medical Research Center, China Medical University Hospital, Taichung City 40447, TaiwanH. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA3D Printing Medical Research Center, China Medical University Hospital, Taichung City 40447, TaiwanHinokitiol is a tropolone-related compound found in heartwood cupressaceous plants. Hinokitiol slows the growth of a variety of cancers through inhibition of cell proliferation. The low water solubility of hinokitiol leads to less bioavailability. This has been highlighted as a major limiting factor. In this study, mesoporous calcium silicate (MCS) nanoparticles, both pure and hinokitiol-loaded, were synthesized and their effects on A549 cells were analyzed. The results indicate that Hino-MCS nanoparticles induce apoptosis in higher concentration loads (>12.5 μg/mL) for A549 cells. Hino-MCS nanoparticles suppress gene and protein expression levels of multiple drug resistance protein 1 (MDR1). In addition, both the activity and the expression levels of caspase-3/-9 were measured in Hino-MCS nanoparticle-treated A549 cells. The Hino-MCS nanoparticles-triggered apoptosis was blocked by inhibitors of pan-caspase, caspase-3/-9, and antioxidant agents (N-acetylcysteine; NAC). The Hino-MCS nanoparticles enhance reactive oxygen species production and the protein expression levels of caspase-3/-9. Our data suggest that Hino-MCS nanoparticles trigger an intrinsic apoptotic pathway through regulating the function of MDR1 and the production of reactive oxygen species in A549 cells. Therefore, we believe that Hino-MCS nanoparticles may be efficacious in the treatment of drug-resistant human lung cancer in the future.http://www.mdpi.com/1996-1944/9/5/306mesoporous calcium silicatehinokitiolapoptosismultiple drug resistance protein 1caspase-3/-9 |
| spellingShingle | Yu-Fang Shen Chia-Che Ho Ming-You Shie Kan Wang Hsin-Yuan Fang Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma Cells Materials mesoporous calcium silicate hinokitiol apoptosis multiple drug resistance protein 1 caspase-3/-9 |
| title | Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma Cells |
| title_full | Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma Cells |
| title_fullStr | Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma Cells |
| title_full_unstemmed | Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma Cells |
| title_short | Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma Cells |
| title_sort | hinokitiol loaded mesoporous calcium silicate nanoparticles induce apoptotic cell death through regulation of the function of mdr1 in lung adenocarcinoma cells |
| topic | mesoporous calcium silicate hinokitiol apoptosis multiple drug resistance protein 1 caspase-3/-9 |
| url | http://www.mdpi.com/1996-1944/9/5/306 |
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