A novel bakuchiol aminoguanidine derivative induces apoptosis in human triple-negative breast cancer cells. / æ°å补骨èé
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Zhejiang Da Xue Xue Bao Yi Xue Ban
; 53(4): 509-518, 2024 Aug 25.
Article
en En, Zh
| MEDLINE
| ID: mdl-39183056
ABSTRACT
OBJECTIVES:
To synthesize new bakuchiol aminoguanidine derivatives and test their effect on viability and apoptosis of human triple-negative breast cancer (TNBC) cells.METHODS:
Two bakuchiol derivatives 1 and 2 were obtained by formylation and Shiff base reaction of bakuchol. The structures of derivatives 1 and 2 were identified by 1H-NMR, 13C-NMR, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) analysis. Human TNBC MDA-MB-231 cells were treated with bakuchiol and its derivatives and cell viability was measured by MTT assay. Apoptosis was detected by fluorescence microscopy and flow cytometry with Annexin V-FITC/PI staining. The expressions of apoptosis-related proteins were analyzed with Western blotting. The JC-1 and reactive oxygen species (ROS) assay kits were used to determine the effect of new bakuchiol derivatives on mitochondrial function.RESULTS:
Based on spectroscopic analysis, a new bakuchiol schiff base derivative was elucidated as 2-{(E)-5-[(S, E)-3, 7-dimethyl-3-vinylocta-1, 6-dien-1-yl]-2-hydroxylbenzylidene} hydrazine-1-carboximidamide (derivative 2). Bakuchiol and its derivatives 1 and 2 all showed cytotoxic activity against the MDA-MB-231 cells. Derivative 2 exhibited the most potent cytotoxic activity to MDA-MB-231 cell with IC50 of (13.11±1.09), (6.91±1.78), and (2.23±1.32) µmol/L after 24, 48, and 72 h. It had low toxicity to normal mouse liver (AML-12) cells with IC50 of (31.23±1.58) µmol/L at 72 h. Fluorescence microscopy and flow cytometry demonstrated apoptosis in breast cancer cells after treating with derivative 2 in a concentration dependent manner. Western blotting showed that after derivative 2 treatment, the expression of apoptosis-related proteins cytochrome C, cleaving caspase-3 and Bax/Bcl-2 radio in MDA-MB-231 cells increased; in addition, apoptosis was associated with the decreased mitochondrial membrane potential and increased reactive oxygen species accumulation.CONCLUSIONS:
The novel bakuchiol aminoguanidine derivative (derivative 2) is capable of inducing apoptosis in MDA-MB-231 cells, but has low toxicity to normal liver cells, suggesting that it may be used as a lead compound for an anti-TNBC agent.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fenoles
/
Especies Reactivas de Oxígeno
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Apoptosis
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Neoplasias de la Mama Triple Negativas
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Guanidinas
Límite:
Female
/
Humans
Idioma:
En
/
Zh
Año:
2024
Tipo del documento:
Article