Liposome-Encapsulated Bacillus Calmette-Guerin Cell Wall Skeleton Enhances Antitumor Efficiency for Bladder Cancer In Vitro and In Vivo via Induction of AMP-Activated Protein Kinase
DC Field | Value | Language |
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dc.contributor.author | Whang, Young Mi | - |
dc.contributor.author | Yoon, Da Hyeon | - |
dc.contributor.author | Hwang, Gwang Yong | - |
dc.contributor.author | Yoon, Hoyub | - |
dc.contributor.author | Park, Serk In | - |
dc.contributor.author | Choi, Young Wook | - |
dc.contributor.author | Chang, In Ho | - |
dc.date.accessioned | 2021-08-30T06:40:45Z | - |
dc.date.available | 2021-08-30T06:40:45Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2020-12 | - |
dc.identifier.issn | 2072-6694 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/51261 | - |
dc.description.abstract | Simple Summary We engineered novel nanoparticles consisting of liposome-encapsulated Bacillus Calmette-Guerin cell well skeleton (BCG-CWS) for intravesical instillation in bladder cancer. The liposome-encapsulated BCG-CWS nanoparticles had antitumoral effects in an orthotopic bladder cancer mouse model, and the BCG-CWS nanoparticles can be further developed as a non-toxic substitute for live BCG with improved dispensability, stability, and size compatibility. This is significant because we succeeded in the intravesical delivery of BCG-CWS through the intravesical route using a catheter in an orthotopic bladder cancer mouse model to specifically target tumor cells. This is the first study on the BCG-CWS-induced activation of AMPK in urothelial carcinoma cells, suggesting that AMPK-mediated reactive oxygen species (ROS) production and ER stress is a cellular signaling pathway in tumors sensitive to BCG-CWS. These results have the potential for significant ramifications in targeted therapy using a predictive marker for bladder cancer. The Mycobacterium Bacillus Calmette-Guerin cell wall skeleton (BCG-CWS), the main immune active center of BCG, is a potent candidate non-infectious immunotherapeutic drug and an alternative to live BCG for use against urothelial carcinoma. However, its application in anticancer therapy is limited, as BCG-CWS tends to aggregate in both aqueous and non-aqueous solvents. To improve the internalization of BCG-CWS into bladder cancer cells without aggregation, BCG-CWS was nanoparticulated at a 180 nm size in methylene chloride and subsequently encapsulated with conventional liposomes (CWS-Nano-CL) using an emulsified lipid (LEEL) method. In vitro cell proliferation assays showed that CWS-Nano-CL was more effective at suppressing bladder cancer cell growth compared to nonenveloped BCG-CWS. In an orthotopic implantation model of luciferase-tagged MBT2 bladder cancer cells, encapsulated BCG-CWS nanoparticles could enhance the delivery of BCG-CWS into the bladder and suppress tumor growth. Treatment with CWS-Nano-CL induced the inhibition of the mammalian target of rapamycin (mTOR) pathway and the activation of AMP-activated protein kinase (AMPK) phosphorylation, leading to apoptosis, both in vitro and in vivo. Furthermore, the antitumor activity of CWS-Nano-CL was mediated predominantly by reactive oxygen species (ROS) generation and AMPK activation, which induced endoplasmic reticulum (ER) stress, followed by c-Jun N-terminal kinase (JNK) signaling-mediated apoptosis. Therefore, our data suggest that the intravesical instillation of liposome-encapsulated BCG-CWS nanoparticles can facilitate BCG-CW cellular endocytosis and provide a promising drug-delivery system as a therapeutic strategy for BCG-mediated bladder cancer treatment. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.subject | APOPTOSIS RESPONSE-4 PAR-4 | - |
dc.subject | HUMAN DENDRITIC CELLS | - |
dc.subject | LUNG-CANCER | - |
dc.subject | BCG-CWS | - |
dc.subject | IMMUNOTHERAPY | - |
dc.subject | THERAPY | - |
dc.subject | CARCINOMA | - |
dc.subject | AUTOPHAGY | - |
dc.subject | STRESS | - |
dc.title | Liposome-Encapsulated Bacillus Calmette-Guerin Cell Wall Skeleton Enhances Antitumor Efficiency for Bladder Cancer In Vitro and In Vivo via Induction of AMP-Activated Protein Kinase | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Park, Serk In | - |
dc.identifier.doi | 10.3390/cancers12123679 | - |
dc.identifier.scopusid | 2-s2.0-85098508220 | - |
dc.identifier.wosid | 000601840600001 | - |
dc.identifier.bibliographicCitation | CANCERS, v.12, no.12 | - |
dc.relation.isPartOf | CANCERS | - |
dc.citation.title | CANCERS | - |
dc.citation.volume | 12 | - |
dc.citation.number | 12 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | APOPTOSIS RESPONSE-4 PAR-4 | - |
dc.subject.keywordPlus | HUMAN DENDRITIC CELLS | - |
dc.subject.keywordPlus | LUNG-CANCER | - |
dc.subject.keywordPlus | BCG-CWS | - |
dc.subject.keywordPlus | IMMUNOTHERAPY | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | CARCINOMA | - |
dc.subject.keywordPlus | AUTOPHAGY | - |
dc.subject.keywordPlus | STRESS | - |
dc.subject.keywordAuthor | AMP activated protein kinase (AMPK) | - |
dc.subject.keywordAuthor | reactive oxygen species (ROS) | - |
dc.subject.keywordAuthor | endoplasmic reticulum (ER) stress | - |
dc.subject.keywordAuthor | bladder cancer | - |
dc.subject.keywordAuthor | orthotopic bladder cancer mouse model | - |
dc.subject.keywordAuthor | BCG-CWS drug-delivery system | - |
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