Thiophenol-formaldehyde triazole causes apoptosis induction in ovary cancer cells and prevents tumor growth formation in mice model
Authors: Lihui Si
Qing Yu
Yan Jia
Ruixin Lin
Hongjuan Jin
Shuli Yang
Wenwen Jian
Journal: European Journal of Medicinal Chemistry (2019)
Discipline: CHEMISTRY
Keywords: Heterocyclic; Macrophages; Metastasis; Migration; Pharmacophore.
Affiliations: Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China., Department of Hepatopancreatobiliary Surgery, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China., Department of Plastic and Aesthetic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China., Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China. Electronic address: .

Abstract:  In the present study a library of thiophenol-formaldehyde-triazole (TFT) derivatives was synthesized and screened against CAOV3, CAOV4 and ES-2 ovary cancer cell lines. Initial screening revealed that five-compounds 5a, 5b, 5j, 5h and 5i inhibited the viability of tested cell lines. Analysis of apoptosis revealed that increase in compound 5a (most active) concentration from 0.25 to 2.0 μM enhanced apoptotic cell proportion. Transwell assay showed reduction in invasive potential of CAOV3 cells on treatment with compound 5a. In wound healing assay increasing the concentration of compound 5a from 0.5 to 2.0 μM caused a significant (P &lt; 0.05) decrease in the migration potential. Western blotting showed that compound 5a treatment markedly decreased the level of matrix metalloproteinase (MMP)-2 and -9 in CAOV3 cells. Treatment of CAOV3 cells with compound 5a caused a marked decrease in Focal Adhesion Kinase (FAK) activation. Tumor growth was inhibited in the compound 5a treated mice markedly than those of untreated group. The tumor metastasis to liver, intestine, spleen and peritoneal cavity was markedly decreased in mice treated with 10 mg/kg dose of compound 5a. Examination of Von Willebrand factor (vWF) expression in liver, intestinal and pulmonary lesions showed a marked decrease in the compound 5a-treated mice. The infiltration of macrophages in the metastatic lesions showed a significant decrease in compound 5a-treated mice. In conclusion, the compound 5a inhibited ovary cancer cell viability and induced apoptosis through decrease in expression of vWF and metalloproteinase, suppression of FAK activation and decrease in infiltration of macrophages. The compound 5a therefore can be investigated further for the treatment of ovary cancer. 

Retracted: No

PubPeer comments:
 Fig 3.  Compound 5a treatment leads to nuclear fragmentation in CAOV3 cells. (A) The cells after compound 5a-treatment were analysed for nuclear morphology using Hoechst 33342 staining by a fluorescent microscope. ![file] Many repeated cells and clusters of cells (with modifications). , 
 Fig 6.  Effect of compound 5a on migration of CAOV3 cells. The cell incubation with compound 5a for 48 h was followed by assessment of migration potential by wound healing assay . Some of these images appear to have crystallised. I have marked a few of the most obvious repetitions. ![file] , 
 Fig 8.  Compound 5a inhibits vWF expression in tumor metastasis lesions. The vWF expression was examined in the lesions extracted from liver, lungs, intestinal and peritoneal tissues. More crystallisation. ![file] , 
 #3 ![file] , 
 Fig 5.  Effect of compound 5a on invasion of CAOV3 cells. The cell incubation with compound 5a was followed by assessment of invasion potential by Transwell method . I have concerns. ![file] ,