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Tytuł pozycji:

A novel selective mitochondrial-targeted curcumin analog with remarkable cytotoxicity in glioma cells.

Tytuł:
A novel selective mitochondrial-targeted curcumin analog with remarkable cytotoxicity in glioma cells.
Autorzy:
Shi L; Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, First People's Hospital of Kunshan, Suzhou, 215300, PR China.
Gao LL; Department of Oncology, The People's Hospital of Funing County in Yancheng City, Yancheng, 224400, Jiang Su, PR China.
Cai SZ; Department of Child and Adolescent Healthcare, Children's Hospital of Soochow University, Suzhou, Suzhou, 215021, PR China. Electronic address: .
Xiong QW; Department of Surgery, Children's Hospital of Soochow University, Suzhou, 215021, PR China.
Ma ZR; Department of Surgery, Children's Hospital of Soochow University, Suzhou, 215021, PR China. Electronic address: .
Źródło:
European journal of medicinal chemistry [Eur J Med Chem] 2021 Oct 05; Vol. 221, pp. 113528. Date of Electronic Publication: 2021 May 12.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Publication: Paris : Editions Scientifiques Elsevier
Original Publication: Paris, S.E.C.T. [etc.]
MeSH Terms:
Antineoplastic Agents/*pharmacology
Brain Neoplasms/*drug therapy
Curcumin/*pharmacology
Glioma/*drug therapy
Mitochondria/*drug effects
Animals ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Apoptosis/drug effects ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Curcumin/chemical synthesis ; Curcumin/chemistry ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Glioma/metabolism ; Glioma/pathology ; Humans ; Mitochondria/metabolism ; Molecular Structure ; Rats ; Structure-Activity Relationship ; Tumor Cells, Cultured
Contributed Indexing:
Keywords: Curcumin; Demethoxycurcumin; Glioma; Mitochondrial-targeting; Thioredoxin reductase
Substance Nomenclature:
0 (Antineoplastic Agents)
IT942ZTH98 (Curcumin)
Entry Date(s):
Date Created: 20210521 Date Completed: 20210806 Latest Revision: 20210806
Update Code:
20240104
DOI:
10.1016/j.ejmech.2021.113528
PMID:
34020339
Czasopismo naukowe
Naturally occurring polyphenol curcumin (4) or demethoxycurcumin (5) and their synthetic derivatives display promising anticancer activities. However, their further development is limited by low bioavailability and poor selectivity. Thus, a mitochondria-targeted compound 14 (DMC-TPP) was prepared in the present study by conjugating a triphenylphosphine moiety to the phenolic hydroxyl group of demethoxycurcumin to enhance its bioavailability and treatment efficacy. The in vitro biological experiments of DMC-TPP showed that it not only displayed higher cytotoxicity as compared with its parent compound 5, but also exhibited superior mitochondria accumulation ability. Glioma cells were more sensitive to DMC-TPP, which inhibited the proliferation of U251 cells with an IC 50 of 0.42 μM. The mechanism studies showed that DMC-TPP triggers mitochondria-dependent apoptosis, caused by caspase activation, production of reactive oxygen species (ROS) and decrease of mitochondrial membrane potential (MMP). In addition, DMC-TPP efficiently inhibited cellular thioredoxin reductase, which contributed to its cytotoxicity. Significantly, DMC-TPP delayed tumor progression in a mouse xenograft model of human glioma cancer. Taken together, the potent in vitro and in vivo antitumor activity of DMC-TPP warrant further comprehensive evaluation as a novel anti-glioma agent.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

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