Xiaozhi Qiao,Yunlan Li,Jiaqi Mai,Xiaoqing Ji,Qingshan Li
Dibutyltin dilaurate (DBTD) has multiple applications in daily life. However, DBTD is easily deposited in the liver and affects liver functions. This study was designed to explore the effects of DBTD on triglyceride metabolism in human normal hepatocyte HL7702 cells. Our results showed that the intracellular fat contents were dose-dependently decreased by DBTD. The expression of lipolysis genes and proteins were elevated while the lipogenesis genes and proteins were diminished by DBTD. The phosphorylation levels of ribosomal S6 kinase 1 were reduced by both rapamycin and DBTD, indicating that the mTOR pathway was suppressed possibly. The decreased sterol regulatory element-binding protein 1C (SREBP1C) transcription levels, as well as the increased peroxisome proliferator-activated receptor alpha (PPARα) transcription levels, caused by rapamycin and DBTD corresponded to the inactive mTOR pathway. In conclusion, it was possible that DBTD reduced the intracellular triglyceride through depressing the mTOR pathway and affecting its downstream transcription factors.Keywords:dibutyltin dilaurate (DBTD);triglycerides metabolism;mTOR pathway;SREBP1C;PPARα
Wei Tian,Wen Zhong,Zengyan Yang,Ling Chen,Shijie Lin,Yanping Li,Yuxing Wang,Peilin Yang,Xing Long
A series of novel dibutyltin complexes based on salen-like ligands ( S01 – S03 ) were synthesized and characterized using ultraviolet-visible spectra，infrared spectra, 1 H, 13 C, and 119 Sn nuclear magnetic resonance, high-resolution mass spectrometry, X-ray crystallography, and thermogravimetric analysis . Complex S03 had excellent anticancer activity in vitro (IC 50 = 1.5 ± 0.2 μM in CAL-27 cell lines), which highly activated ROS expression levels and induced apoptosis and cell cycle arrest at the G2/M phase. Interestingly, complex S03 induced cancer cell death through multiple mechanisms (mitochondrial pathway, ER-stress pathway, and DNA damage pathway). This study reveals new mechanisms of organotin complexes and provides new insights into the development of organotin metal complexes as anticancer drugs in the future, and compounds with multiple anticancer mechanisms may be a new strategy for delaying or overcoming drug resistance to chemotherapy and target therapy.
Three series of (dimethyl-, dibutyl-, and diphenyl-) new organotin(IV) complexes based on chlorine substituted aryl ligands were synthesized and characterized by UV, 1 H NMR, 13 C NMR, 119 Sn NMR, HRMS, and X-ray crystallography analysis. MTT results showed that chlorine substitution at different positions on the aryl group exhibited different anticancer activities. Among them, 5-chloro substituents > 3,5-dichloro substituents > 3-chloro substituents on the aryl ring of salicylaldehyde on Schiff base ligand. In addition, different substituents on the tin atom also demonstrated extreme differences in anticancer activities, where dibutyltin > diphenyltin > dimethyltin. Interestingly, the complex LTDB2 exhibited excellent anti-proliferative activity against breast cancer MDA-MB-231 cells (superior to cisplatin) and lower toxicity against human embryonic kidney HEK-293 cells in vitro. Flow cytometry showed that LTDB2 not only induced apoptosis, but also induced cell cycle arrest in G2 phase. These findings provide new insights for further research and development of novel organotin(IV) complexes as anticancer drugs. Complex LTDB2 exhibited excellent anti-proliferative activity against breast cancer MDA-MB-231 cells in vitro and was superior to cisplatin. Flow cytometry showed that LTDB2 not only induced apoptosis, but also induced cell cycle arrest in G2 phase.
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