Hydrazinyldiene-chroman-2,4-diones in inducing growth arrest and apoptosis in breast cancer cells: Synergism with doxorubicin and correlation with physicochemical properties

Abstract

This study evaluates the effects of previously synthesized hydrazinyldiene-chroman-2,4-diones on cell proliferation and apoptosis, cell cycle distribution and migration capacity of MCF-7 breast cancer cells in synergy with doxorubicin. Physicochemical properties of the synthesized compounds were correlated with their structure and activity. Significant cell viability decrease in comparison with the effect of doxorubicin alone and the reference 4-hydroxycoumarin was observed when combination treatment comprising doxorubicin and the title compounds was applied. Synergistic effect with doxorubicin was also observed in down-regulation of phospho-Thr 308Akt levels, confirming reduced proliferation and increased apoptosis. Combined treatment increased the percentage of cells arrested at the G 2 /M stage. Additive inhibition of cell migration was also observed, pointing to the possibility of reducing the risk of metastases. With their solubility profile and log D 7.4 , all the synthesized compounds follow Lipinski's rule of five for good permeability (absorption) potential.

Crizotinib induces apoptosis and gene expression changes in ALK+ anaplastic large cell lymphoma cell lines; brentuximab synergizes and doxorubicin antagonizes

“…The mechanisms of doxorubicin's antineoplastic effect are complex and incompletely understood, but include the intercalation of DNA, the inhibition of topoisomerase II, and the production of free radicals, leading to apoptosis, autophagy, senescence, necrosis, and mitochondrial dysfunction, with some gene response effects . Cell death is, to at least some extent, cell cycle dependent and involves arrest in the G2/M stage . The relative resistance of Karpas 299 to doxorubicin could be related to TP53 mutation in that line as well as possibly to multidrug resistance gene ABCC1 expression .…”

“…62,63 Cell death is, to at least some extent, cell cycle dependent and involves arrest in the G2/M stage. 64 The relative resistance of Karpas 299 to doxorubicin could be related to TP53 mutation in that line as well as possibly to multidrug resistance gene ABCC1 expression. [65][66][67] The fact that Karpas 299 shows different gene expression patterns than others opens the possibility that expression analysis may be useful to identify drug resistance.…”

<p>Brevilin A Inhibits STAT3 Signaling and Induces ROS-Dependent Apoptosis, Mitochondrial Stress and Endoplasmic Reticulum Stress in MCF-7 Breast Cancer Cells</p>

“…Breast cancer, a heterogeneous disease, is diagnosed in over one million new patients every year which accounts for 23% of total new cases, 16% of all female cancers and 18% of total deaths related to cancer in both males and females. 1,2 Incidence and prevalence rate of breast cancer is higher in North America, Northern and Western Europe, New Zealand and Australia compared to Eastern Asia. 3 In China, however, the incidence rate of breast cancer has increased in last three decades by 20 to 30% and, according to Chinese urban cancer registries, it amounts about 3-5% each year.…”

Bis(4-hydroxy-2H-chromen-2-one) Coumarin Induces Apoptosis in MCF-7 Human Breast Cancer Cells Through Aromatase Inhibition

“…In recent years, a significant number of coumarin derivatives have been studied as potential agents for cancer therapy (4), particularly in breast cancer (5). Depending on their structure, they can inhibit tumor necrosis factor-alpha (TNFα) production, cell cycle and aromatase activities or induce apoptosis through the activation of caspases (6,7). Special attention has been devoted to the new synthetic bis(4-hydroxy-2H-chromen-2one) coumarin, named 4HC, which has been reported to inhibit proliferation and to promote cell death in tumor cell lines (8).…”