Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells.

Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity.

Changes of [18F]FDG-PET/CT quantitative parameters in tumor lesions by the Bayesian penalized-likelihood PET reconstruction algorithm and its influencing factors.

BACKGROUND: To compare the changes in quantitative parameters and the size and degree of 18F-fluorodeoxyglucose ([18F]FDG) uptake of malignant tumor lesions between Bayesian penalized-likelihood (BPL) and non-BPL reconstruction algorithms. METHODS: Positron emission tomography/computed tomography images of 86 malignant tumor lesions were reconstructed using the algorithms of ordered subset expectation maximization (OSEM), OSEM + time of flight (TOF), OSEM + TOF + point spread function (PSF), and BPL. [18F]FDG parameters of maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and signal-to-background ratio (SBR) of these lesions were measured. Quantitative parameters between the different reconstruction algorithms were compared, and correlations between parameter variation and lesion size or the degree of [18F]FDG uptake were analyzed. RESULTS: After BPL reconstruction, SUVmax, SUVmean, and SBR were significantly increased, MTV was significantly decreased. The difference values of %ΔSUVmax, %ΔSUVmean, %ΔSBR, and the absolute value of %ΔMTV between BPL and OSEM + TOF were 40.00%, 38.50%, 33.60%, and 33.20%, respectively, which were significantly higher than those between BPL and OSEM + TOF + PSF. Similar results were observed in the comparison of OSEM and OSEM + TOF + PSF with BPL. The %ΔSUVmax, %ΔSUVmean, and %ΔSBR were all significantly negatively correlated with the size and degree of [18F]FDG uptake in the lesions, whereas significant positive correlations were observed for %ΔMTV and %ΔTLG. CONCLUSION: The BPL reconstruction algorithm significantly increased SUVmax, SUVmean, and SBR and decreased MTV of tumor lesions, especially in small or relatively hypometabolic lesions.

Design, synthesis, and apoptosis-promoting effect evaluation of novel pyrazole with benzo[d]thiazole derivatives containing aminoguanidine units.

New pyrazole with benzo[d]thiazoles containing hydrazinecarboximidamide substituent was synthesised and evaluated for cytotoxicity and apoptotic activity using the MTT assay, flow cytometry, and Western blot analysis. Among the compounds studied, (E)-2-((1-(6-((4-fluorobenzyl)oxy)benzo[d]thiazol-2-yl)-3-phenyl-1H- pyrazol-4-yl)methylene) hydrazinecarboximidamide (8l) was potent, with IC50 values of 2.41 µM, 2.23 µM, 3.75 µM and 2.31 µM in vitro anti-proliferative activity testing against triple-negative breast cancer cell line MDA-MB-231, non-triple-negative breast cancer MCF-7 cells, and human hepatocarcinoma HepG2 cells, and SMMC-7721 cells, respectively. Especially, the activity against MDA-MB-231 was similar to that of Doxorubicin, which was used as a positive control in this study. Next, the Annexin V/PI flow cytometry assay was used at different concentrations of compound 8l to demonstrate that compound 81 induced apoptosis of MDA-MB-231 cells in a concentration-dependent manner. Finally, these results were further verified by Western blot analysis. Taken together, the results of this study revealed that compound 8l may be a potential anticancer compound play a significant role in the subsequent researches.