Acetylshikonin, A Novel CYP2J2 Inhibitor, Induces Apoptosis in RCC Cells via FOXO3 Activation and ROS Elevation.
Journal
Oxidative medicine and cellular longevity
ISSN: 1942-0994
Titre abrégé: Oxid Med Cell Longev
Pays: United States
ID NLM: 101479826
Informations de publication
Date de publication:
2022
2022
Historique:
received:
18
08
2021
revised:
02
12
2021
accepted:
17
02
2022
entrez:
21
3
2022
pubmed:
22
3
2022
medline:
5
4
2022
Statut:
epublish
Résumé
Acetylshikonin is a shikonin derivative originated from Lithospermum erythrorhizon roots that exhibits various biological activities, including granulation tissue formation, promotion of inflammatory effects, and inhibition of angiogenesis. The anticancer effect of acetylshikonin was also investigated in several cancer cells; however, the effect against renal cell carcinoma (RCC) have not yet been studied. In this study, we aimed to investigate the anticarcinogenic mechanism of acetylshikonin in A498 and ACHN, human RCC cell lines. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide), cell counting, and colony forming assay showed that acetylshikonin induced cytotoxic and antiproliferative effects in a dose- and time-dependent manner. Cell cycle analysis and annexin V/propidium iodide (PI) double staining assay indicated the increase of subG1 phase and apoptotic rates. Also, DNA fragmentation was observed by using the TUNEL and comet assays. The intracellular ROS level in acetylshikonin-treated RCC was evaluated using DCF-DA. The ROS level was increased and cell viability was decreased in a dose- and time-dependent manner, while those were recovered when cotreated with NAC. Western blotting analysis showed that acetylshikonin treatment increased the expression of FOXO3, cleaved PARP, cleaved caspase-3, -6, -7, -8, -9,
Identifiants
pubmed: 35308176
doi: 10.1155/2022/9139338
pmc: PMC8926475
doi:
Substances chimiques
Anthraquinones
0
FOXO3 protein, human
0
Forkhead Box Protein O3
0
Reactive Oxygen Species
0
Cytochrome P-450 CYP2J2
EC 1.14.14.1
acetylshikonin
ST04094S3X
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9139338Informations de copyright
Copyright © 2022 Heui Min Lim et al.
Déclaration de conflit d'intérêts
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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