Biological Evaluation in Resistant Cancer Cells and Study of Mechanism of Action of Arylvinyl-1,2,4-Trioxanes
DC Field | Value | Language |
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dc.contributor.author | Ng, Jerome P. L. | - |
dc.contributor.author | Tiwari, Mohit K. | - |
dc.contributor.author | Nasim, Ali Adnan | - |
dc.contributor.author | Zhang, Rui Long | - |
dc.contributor.author | Qu, Yuanqing | - |
dc.contributor.author | Sharma, Richa | - |
dc.contributor.author | Law, Betty Yuen Kwan | - |
dc.contributor.author | Yadav, Dharmendra K. | - |
dc.contributor.author | Chaudhary, Sandeep | - |
dc.contributor.author | Coghi, Paolo | - |
dc.contributor.author | Wong, Vincent Kam Wai | - |
dc.date.accessioned | 2022-04-13T03:40:22Z | - |
dc.date.available | 2022-04-13T03:40:22Z | - |
dc.date.created | 2022-04-13 | - |
dc.date.issued | 2022-03 | - |
dc.identifier.issn | 1424-8247 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/83965 | - |
dc.description.abstract | 1,2,4-trioxane is a pharmacophore, which possesses a wide spectrum of biological activities, including anticancer effects. In this study, the cytotoxic effect and anticancer mechanism of action of a set of 10 selected peroxides were investigated on five phenotypically different cancer cell lines (A549, A2780, HCT8, MCF7, and SGC7901) and their corresponding drug-resistant cancer cell lines. Among all peroxides, only 7 and 8 showed a better P-glycoprotein (P-gp) inhibitory effect at a concentration of 100 nM. These in vitro results were further validated by in silico docking and molecular dynamic (MD) studies, where compounds 7 and 8 exhibited docking scores of -7.089 and -8.196 kcal/mol, respectively, and remained generally stable in 100 ns during MD simulation. Further experiments revealed that peroxides 7 and 8 showed no significant effect on ROS accumulations and caspase-3 activity in A549 cells. Peroxides 7 and 8 were also found to decrease cell membrane potential. In addition, peroxides 7 and 8 were demonstrated to oxidize a flavin cofactor, possibly elucidating its mechanism of action. In conclusion, apoptosis induced by 1,2,4-trioxane was shown to undergo via a ROS- and caspase-3-independent pathway with hyperpolarization of cell membrane potential. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.relation.isPartOf | PHARMACEUTICALS | - |
dc.title | Biological Evaluation in Resistant Cancer Cells and Study of Mechanism of Action of Arylvinyl-1,2,4-Trioxanes | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000774315900001 | - |
dc.identifier.doi | 10.3390/ph15030360 | - |
dc.identifier.bibliographicCitation | PHARMACEUTICALS, v.15, no.3 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85127547268 | - |
dc.citation.title | PHARMACEUTICALS | - |
dc.citation.volume | 15 | - |
dc.citation.number | 3 | - |
dc.contributor.affiliatedAuthor | Yadav, Dharmendra K. | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | 1,2,4-trioxanes | - |
dc.subject.keywordAuthor | P-glycoprotein | - |
dc.subject.keywordAuthor | anticancer | - |
dc.subject.keywordAuthor | molecular docking | - |
dc.subject.keywordAuthor | mechanism of action | - |
dc.subject.keywordPlus | P-GLYCOPROTEIN | - |
dc.subject.keywordPlus | LUNG-CANCER | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | ARTEMISININ | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | 1,2,4-TRIOXANES | - |
dc.subject.keywordPlus | ARTESUNATE | - |
dc.subject.keywordPlus | INDUCTION | - |
dc.subject.keywordPlus | EFFLUX | - |
dc.subject.keywordPlus | HEME | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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