A novel bakuchiol aminoguanidine derivative induces apoptosis in human triple-negative breast cancer cells
10.3724/zdxbyxb-2024-0070
- VernacularTitle:新型补骨脂酚氨基胍衍生物诱导人三阴性乳腺癌细胞凋亡
- Author:
Zhenhai ZHANG
1
;
Jing ZHU
;
Jian'an WANG
;
Jie CHEN
;
Yingying PANG
;
Chengzhu WU
Author Information
1. 蚌埠医科大学第一附属医院急诊外科,安徽 蚌埠 233004
- Keywords:
Bakuchiol;
Aminoguanidine;
Triple-negative breast cancer;
Apoptosis;
Mitochondrial function
- From:
Journal of Zhejiang University. Medical sciences
2024;53(4):509-518
- CountryChina
- Language:Chinese
-
Abstract:
Objective: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.Conclusion: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.
