Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment

Cannabidiol (CBD), a primary bioactive phytocannabinoid extracted from hemp, is reported to possess potent anti-tumorigenic activity in multiple cancers. However, the effects of CBD on bladder cancer (BC) and the underlying molecular mechanisms are rarely reported. Here, several experiments proved t...

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Main Authors: Shanshan Chen, Changping Deng, Wenyun Zheng, Shihui Li, Yuping Liu, Tong Zhang, Chen Zhang, Yunhui Fu, Hui Miao, Fuzheng Ren, Xingyuan Ma
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/13/9/1415
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author Shanshan Chen
Changping Deng
Wenyun Zheng
Shihui Li
Yuping Liu
Tong Zhang
Chen Zhang
Yunhui Fu
Hui Miao
Fuzheng Ren
Xingyuan Ma
author_facet Shanshan Chen
Changping Deng
Wenyun Zheng
Shihui Li
Yuping Liu
Tong Zhang
Chen Zhang
Yunhui Fu
Hui Miao
Fuzheng Ren
Xingyuan Ma
author_sort Shanshan Chen
collection DOAJ
description Cannabidiol (CBD), a primary bioactive phytocannabinoid extracted from hemp, is reported to possess potent anti-tumorigenic activity in multiple cancers. However, the effects of CBD on bladder cancer (BC) and the underlying molecular mechanisms are rarely reported. Here, several experiments proved that CBD promoted BC cells (T24, 5637, and UM-UC-3) death. For example, T24 cells were treated with 12 µM CBD for 48 h, flow cytometry analysis demonstrated that early and late apoptotic cells were accounted for by 49.91%, indicating CBD enhanced cell apoptosis ability. To deeper explore molecular mechanisms, the CBD-treated T24 cell transcriptome libraries were established. KEGG analysis implied that the significantly changed genes were enriched in the PI3K/Akt pathway. qRT-PCR and Western blot assays verified that CBD regulated BC cells growth and migration and induced apoptosis by inactivating the PI3K/Akt pathway. Meanwhile, the developed chitosan to wrap CBD-loaded PLGA nanoparticles can significantly enhance the adhesion of the material to the mouse bladder wall, and the binding efficiency of mucin to chitosan-PLGA nanoparticles reached 97.04% ± 1.90%. In summary, this work demonstrates that CBD may become a novel reliable anticancer drug and the developed intravesical adhesion system is expected to turn into a potential means of BC chemotherapy drug delivery.
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spelling doaj.art-aa1a221881eb45fa8495442d192661932023-11-22T14:47:26ZengMDPI AGPharmaceutics1999-49232021-09-01139141510.3390/pharmaceutics13091415Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for TreatmentShanshan Chen0Changping Deng1Wenyun Zheng2Shihui Li3Yuping Liu4Tong Zhang5Chen Zhang6Yunhui Fu7Hui Miao8Fuzheng Ren9Xingyuan Ma10Laboratory of Biopharmaceutical and Cell Engineering, School of Biological, East China University of Science and Technology, 130 Meilong Road, P.O. Box No. 365, Shanghai 200237, ChinaLaboratory of Biopharmaceutical and Cell Engineering, School of Biological, East China University of Science and Technology, 130 Meilong Road, P.O. Box No. 365, Shanghai 200237, ChinaShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaLaboratory of Biopharmaceutical and Cell Engineering, School of Biological, East China University of Science and Technology, 130 Meilong Road, P.O. Box No. 365, Shanghai 200237, ChinaShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaLaboratory of Biopharmaceutical and Cell Engineering, School of Biological, East China University of Science and Technology, 130 Meilong Road, P.O. Box No. 365, Shanghai 200237, ChinaLaboratory of Biopharmaceutical and Cell Engineering, School of Biological, East China University of Science and Technology, 130 Meilong Road, P.O. Box No. 365, Shanghai 200237, ChinaLaboratory of Biopharmaceutical and Cell Engineering, School of Biological, East China University of Science and Technology, 130 Meilong Road, P.O. Box No. 365, Shanghai 200237, ChinaShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaLaboratory of Biopharmaceutical and Cell Engineering, School of Biological, East China University of Science and Technology, 130 Meilong Road, P.O. Box No. 365, Shanghai 200237, ChinaCannabidiol (CBD), a primary bioactive phytocannabinoid extracted from hemp, is reported to possess potent anti-tumorigenic activity in multiple cancers. However, the effects of CBD on bladder cancer (BC) and the underlying molecular mechanisms are rarely reported. Here, several experiments proved that CBD promoted BC cells (T24, 5637, and UM-UC-3) death. For example, T24 cells were treated with 12 µM CBD for 48 h, flow cytometry analysis demonstrated that early and late apoptotic cells were accounted for by 49.91%, indicating CBD enhanced cell apoptosis ability. To deeper explore molecular mechanisms, the CBD-treated T24 cell transcriptome libraries were established. KEGG analysis implied that the significantly changed genes were enriched in the PI3K/Akt pathway. qRT-PCR and Western blot assays verified that CBD regulated BC cells growth and migration and induced apoptosis by inactivating the PI3K/Akt pathway. Meanwhile, the developed chitosan to wrap CBD-loaded PLGA nanoparticles can significantly enhance the adhesion of the material to the mouse bladder wall, and the binding efficiency of mucin to chitosan-PLGA nanoparticles reached 97.04% ± 1.90%. In summary, this work demonstrates that CBD may become a novel reliable anticancer drug and the developed intravesical adhesion system is expected to turn into a potential means of BC chemotherapy drug delivery.https://www.mdpi.com/1999-4923/13/9/1415cannabidiol (CBD)bladder cancer (BC)RNA sequencingPI3K/AktchitosanCBD-loaded PLGA
spellingShingle Shanshan Chen
Changping Deng
Wenyun Zheng
Shihui Li
Yuping Liu
Tong Zhang
Chen Zhang
Yunhui Fu
Hui Miao
Fuzheng Ren
Xingyuan Ma
Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment
Pharmaceutics
cannabidiol (CBD)
bladder cancer (BC)
RNA sequencing
PI3K/Akt
chitosan
CBD-loaded PLGA
title Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment
title_full Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment
title_fullStr Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment
title_full_unstemmed Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment
title_short Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment
title_sort cannabidiol effectively promoted cell death in bladder cancer and the improved intravesical adhesion drugs delivery strategy could be better used for treatment
topic cannabidiol (CBD)
bladder cancer (BC)
RNA sequencing
PI3K/Akt
chitosan
CBD-loaded PLGA
url https://www.mdpi.com/1999-4923/13/9/1415
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