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Materials 2016, 9(5), 306; doi:10.3390/ma9050306

Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma Cells

1
3D Printing Medical Research Center, China Medical University Hospital, Taichung City 40447, Taiwan
2
H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
3
Georgia Tech Manufacturing Institute, Georgia Institute of Technology, Atlanta, GA 30332, USA
4
Department of Thoracic Surgery, China Medical University Hospital, Taichung City 40447, Taiwan
5
School of Medicine, China Medical University, Taichung City 40447, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Aldo Boccaccini
Received: 5 February 2016 / Revised: 18 April 2016 / Accepted: 20 April 2016 / Published: 25 April 2016
(This article belongs to the Section Biomaterials)
View Full-Text   |   Download PDF [3007 KB, uploaded 25 April 2016]   |  

Abstract

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. View Full-Text
Keywords: mesoporous calcium silicate; hinokitiol; apoptosis; multiple drug resistance protein 1; caspase-3/-9 mesoporous calcium silicate; hinokitiol; apoptosis; multiple drug resistance protein 1; caspase-3/-9
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Shen, Y.-F.; Ho, C.-C.; Shie, M.-Y.; Wang, K.; Fang, H.-Y. Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma Cells. Materials 2016, 9, 306.

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