A novel β-diiminato manganese^III complex as the promising anticancer agent induces G₀/G₁ cell cycle arrest and triggers apoptosis via mitochondrial-dependent pathways in MCF-7 and MDA-MB-231 human breast cancer cells

Abstract

Breast cancer is the most common cancer in women worldwide. The development of potential metalbased compounds has had a huge impact on cancer chemotherapy. This study was conducted to evaluate the cytotoxic activity of a novel b-diiminato manganese III complex on MCF-7, MDA-MB-231, 184B5, and WRL-68 cells through MTT, LDH, and trypan blue cell viability assay. To investigate the mechanism of its inhibitory and cytotoxic activity initially on breast cancer cells, cell cycle progression was determined using flow cytometry analysis. Apoptosis was also assessed through morphological

A reactive oxygen species-generating, cancer stem cell-potent manganese(ii) complex and its encapsulation into polymeric nanoparticles

“…The cellular mechanism of action of the manganese( ii / iii ) complexes is highly dependent on the nature of the coordinated ligand 25. Notably, a number of studies have shown that manganese metal and its coordination complexes increase markers of oxidative stress in various cell types due to intracellular ROS generation 20,26–29. By utilising manganese over other more common endogenous metals such as copper and iron, we hope to take advantage of the many physiologically accessible oxidation states of manganese and its ability to undergo Fenton-type reactions (whereby the manganese( ii ) form can effectively generate hydroxide radicals from endogenous hydrogen peroxide), to potently kill CSCs via efficient ROS production.…”

In vivo acute toxicity evaluation and in vitro molecular mechanism study of antiproliferative activity of a novel indole Schiff base β-diiminato manganeseIII complex in hormone-dependent and triple negative breast cancer cells

“…To figure out the involvement of caspase cascade events underlying apoptosis process, MCF-7 and MDA-MB-231 cells were stained with aminoluciferin-labeled substrate of caspases and determined the enzymatic activity of caspase-3/7, −8, −9 by quantifying the luminescence intensities in indicated time points and concentrations. As the potential of Mn III complex to induce the ROS generation has been proved in our previous study (Farghadani et al, 2017) and in agreement with other studies revealing that caspase-9 is activated as a downstream target of ROS elevation which is connected with mitochondrial intrinsic pathway (Gao et al, 2015; Hajrezaie et al, 2015; Zheng et al, 2018), incubation with Mn III complex led to enhanced caspase-9 activity in treated MCF-7 and MDA-MB-231 cells representing the involvement of intrinsic pathway in apoptosis induction in both cell lines. Furthermore, there is an evidence that ROS may also cause cellular apoptosis mediated by death receptors which is activated by caspase-8, as an early apoptotic marker and initiator of the extrinsic apoptosis pathway (Redza-Dutordoir & Averill-Bates, 2016).…”

“…The effect of Mn III complex and its ligand, indole Schiff-based tetradentate β-diiminato ligand (LH 3 ), on viability of MCF-7 and MDA-MB-231 cells have determined using the colorimetric MTT assay. LH 3 and Mn III complex displayed growth inhibition properties and reduced the MCF-7 and MDA-MB-231 cell viability in a dose-dependent manner with IC 50 values of 3.51 ± 0.14 and 2.41 ± 0.29 µg/mL for LH 3 and1.44 ± 0.24 and 2.28 ± 0.38 µg/mL for Mn III complex (Farghadani et al, 2017), respectively, after 24 h treatment. In addition, the IC 50 value of chemotherapeutic drug, cisplatin, was 8.94 ± 0.66 µg/mL for MCF-7 cells and 6.79 ± 1.22 µg/mL for MDA-MB-231 cells (Table 2).…”

“…In our previous study (Farghadani et al, 2017), we have demonstrated that treatment with indole Schiff base manganese (Mn) III complex significantly inhibited the proliferation of MCF-7 and MDA-MB-231 cells thought the cell cycle arrest at the G 0 /G 1 phase and apoptosis induction. Henceforth, we have taken a step further and investigated the molecular mechanisms underlying antiproliferative effect of Mn III complex in treated MCF-7 and MDA-MB-231 cells.…”

In Vitro and In Vivo Anticancer Activity of the Most Cytotoxic Fraction of Pistachio Hull Extract in Breast Cancer

“…Also as extracts of plants may activate the immune system of the hosts and kill cancer cells, one can consider testing the concentrations of various cytokines, tumor necrosis factor, etc. [24], before and after administration of PV. On the other hand, since 100% pure gallic acid and quercetin are commercially available, a combination of these two agents at the same concentration ratio as they exist in pistachio can be tested to examine the anti-tumor effect of PV extract.…”