scholarly journals The selective cytotoxicity of silver thiosulfate, a silver complex, on MCF-7 breast cancer cells through ROS-induced cell death

2021 ◽  
Author(s):  
Akira Ota ◽  
Masataka Tajima ◽  
Kazunori Mori ◽  
Erika Sugiyama ◽  
Vilasinee Hirunpanich Sato ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Morphological Changes ◽  
Silver Thiosulfate ◽  
Anticancer Effects ◽  
Ros Accumulation ◽  
Intracellular Ros ◽  
Normal Human ◽  
Mcf 7

Abstract Background Silver is a transition metal that is known to be less toxic than platinum. However, only few studies have reported the anticancer effects of some silver complexes and their possibility as an alternative to platinum complex. This study investigated the anticancer effects of the silver thiosulfate complex (STS), [Ag(S2O3)2]3−, consisting of silver and sodium thiosulfate. Methods In vitro cytotoxic activity of STS was investigated comparatively in human cancer cell lines (K562 and MCF-7) and normal human cells (mesenchymal stem cells and mammary epithelial cells). For its anticancer effects, cell cycle, mode of cell death, morphological changes, and accumulation of intracellular ROS and GSH were evaluated in MCF-7 to provide mechanistic insights. Results STS showed a concentration-dependent cytotoxicity in MCF-7 cell, which was abolished by pretreatment with N-acetylcysteine, suggesting ROS accumulation by STS. Moreover, STS caused cell cycle arrest at the G1 phase, decrease in the GSH levels, and morphological changes in MCF-7. Direct measurement of ROS demonstrated the elevation of intracellular ROS accumulation in cancer cells treated with STS; however, neither cytotoxicity nor ROS accumulation was observed in normal human cells. Conclusion The results obtained here are the first evidence to show that STS exhibited an anticancer activity through ROS-induced mechanisms, and that its cytotoxicity is highly selective to cancer cells. The results of the present study warrant further investigation on the detailed mechanism of STS actions, as well as its in vivo effectiveness and safety for clinical application.

scholarly journals Differential Mechanisms of Cell Death Induced by HDAC Inhibitor SAHA and MDM2 Inhibitor RG7388 in MCF-7 Cells

Cells ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 8 ◽  
Author(s):  
Umamaheswari Natarajan ◽  
Thiagarajan Venkatesan ◽  
Vijayaraghavan Radhakrishnan ◽  
Shila Samuel ◽  
Appu Rathinavelu
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Hdac Inhibitor ◽  
The Other ◽  
Combination Treatments ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Mcf 7

Gene expression is often altered by epigenetic modifications that can significantly influence the growth ability and progression of cancers. SAHA (Suberoylanilide hydroxamic acid, also known as Vorinostat), a well-known Histone deacetylase (HDAC) inhibitor, can stop cancer growth and metastatic processes through epigenetic alterations. On the other hand, Letrozole is an aromatase inhibitor that can elicit strong anti-cancer effects on breast cancer through direct and indirect mechanisms. A newly developed inhibitor, RG7388 specific for an oncogene-derived protein called MDM2, is in clinical trials for the treatment of various cancers. In this paper, we performed assays to measure the effects of cell cycle arrest resulting from individual drug treatments or combination treatments with SAHA + letrozole and SAHA + RG7388, using the MCF-7 breast cancer cells. When SAHA was used individually, or in combination treatments with RG7388, a significant increase in the cytotoxic effect was obtained. Induction of cell cycle arrest by SAHA in cancer cells was evidenced by elevated p21 protein levels. In addition, SAHA treatment in MCF-7 cells showed significant up-regulation in phospho-RIP3 and MLKL levels. Our results confirmed that cell death caused by SAHA treatment was primarily through the induction of necroptosis. On the other hand, the RG7388 treatment was able to induce apoptosis by elevating BAX levels. It appears that, during combination treatments, with SAHA and RG7388, two parallel pathways might be induced simultaneously, that could lead to increased cancer cell death. SAHA appears to induce cell necroptosis in a p21-dependent manner, and RG7388 seems to induce apoptosis in a p21-independent manner, outlining differential mechanisms of cell death induction. However, further studies are needed to fully understand the intracellular mechanisms that are triggered by these two anti-cancer agents.

Cell Cycle Arrest and Apoptosis Induction of Phloroacetophenone Glycosides and Caffeoylquinic Acid Derivatives in Gastric Adenocarcinoma (AGS) Cells

2018 ◽  
Vol 18 (4) ◽  
pp. 610-616 ◽  
Author(s):  
Naser Jafari ◽  
Seyed Jalal Zargar ◽  
Mohammad-Reza Delnavazi ◽  
Narguess Yassa
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Phenolic Compounds ◽  
Chlorogenic Acid ◽  
Cancer Cells ◽  
Morphological Changes ◽  
G1 Phase ◽  
Mrna Levels ◽  
Apoptosis Induction ◽  
Caffeoylquinic Acid

Introduction: In the present study, we analyzed anti-proliferative and apoptosis induction activity of five phenolic compounds: echisoside, pleoside, chlorogenic acid, 4,5-Di-O-caffeoylquinic acid, and cynarin on AGS (adenocarcinoma gastric) cell line. Method: These phenolic compounds were isolated from methanol extract of Dorema glabrum root. An MTT assay was conducted to evaluate the inhibitory effect on cancer cells. EB/AO staining was done to assess the mode of cell death and morphological changes of the cells’ nuclei. Cell cycle distribution of the cells was analyzed by flow cytometry, and for further confirmation of the pathway, mRNA levels of apoptosis cascade players were quantified by qRT-PCR. Result: We found that echisoside, pleoside, chlorogenic acid, 4,5-Di-O-caffeoylquinic acid, and cynarin inhibited the proliferation of AGS cancer cells in vitro. Our data revealed that these compounds triggered morphological changes characteristic of apoptotic cell death. These compounds up-regulated bax and caspase3 expression and down-regulated cyclin D1, bcl2, VEGFA, c-myc and survivin. Moreover, cell population increased at the G1 phase, and a number of cells at the G2/M phase of the cell cycle decreased after treatment. Conclusion: All these data suggest that phenolic compounds have a cytotoxic effect on gastric cancer cells and could trigger apoptosis. Besides cytotoxic activity, they could potentially arrest the cell cycle at the G1 phase.

Patterns of Cell Death Induced by Thiohydantoins in Human MCF-7 Breast Cancer Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Tatiane Renata Fagundes ◽  
Bruna Bortoleti ◽  
Priscila Camargo ◽  
Vírgínia Concato ◽  
Fernanda Tomiotto-Pellissier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Volume ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Breast Tumor Cells ◽  
Mcf 7

Background: Conventional therapies for breast cancer is still a challenge due to use of cytotoxic drugs not highly effective with major adverse effects. Thiohydantoins, are biologically active heterocyclic compounds reported by several biological activities, including anticarcinogenic properties, i.e., this work aimed to assess the use of thiohydantoin as a potential antitumor agent against MCF-7 breast cancer cells. Methods: MTT and neutral red assays were used to assess the possible cytotoxic activity of compounds against MCF-7 cells. Cell volume measurement and analysis were performed by flow cytometry, fluorescence analysis was carried out to determine patterns of cell death induced by thiohydantoins. Results: The treatment with micromolar doses of thiohydantoins promoted a decrease in the viability of MCF-7 breast tumor cells. Also were observed the increase in ROS and NO production, reduction in cell volume, loss of membrane integrity, mitochondrial depolarization, and increased fluorescence for annexin V and caspase-3. These findings indicate cell death by apoptosis and increased formation of autophagic vacuoles and stopping the cell cycle in the G1/ G0 phase. Conclusions: Our results indicate that thiohydantoins are cytotoxic to breast tumor cells, and this effect is linked to the increase in ROS production. This phenomenon changes tumorigenic pathways, that lead to a halt of the cell cycle in G1/G0, an important checkpoint for DNA errors, which may have altered the process by which cells produce energy, causing a decrease in mitochondrial viability and thus leading to the apoptotic process. Furthermore, the results indicate increased autophagy, a vital process linked to a decrease in lysosomal viability and considered as a cell death and tumor suppression mechanism.

Evaluation of Cytotoxic Mechanisms of Clinacanthus Nutans Extracts in Cancer Cells

2020 ◽  
Vol 10 ◽  
Author(s):  
Nurul Atiqah Sulaiman ◽  
Rajan Rajabalaya ◽  
Shirley Huan Fang Lee ◽  
Ya Chee Lim ◽  
Wei Hon Lim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Annexin V ◽  
Cell Cycle Profile ◽  
Clinacanthus Nutans ◽  
Mcf 7

Background: Commercially available Clinacanthus nutans (Burm.F) Lindau (Acanthaceae) (CN) leaf preparations are gaining attention as an alternative cancer treatment, particularly in South East Asia. Multiple studies have suggested that CN has potential anticancer activities; however, the mechanism of these activities has remained elusive. Objective: This study evaluated the cytotoxic mechanisms of CN extracts in cancer cells. Methods: CN extracts were prepared from either fresh or dried leaves, using different solvents. Cytotoxicity of CN extracts were tested on the A549 (lung cancer), HeLa (cervical cancer), MCF-7 (breast cancer) and MDA-MB-231 (breast cancer) cell lines using the MTT assay. Flow cytometry was used to assess changes in the cell cycle profile, while Western blotting was used to examine microtubule stability. Finally, the mode of cell death was investigated using the Annexin V-FITC Apoptosis Detection Kit. Results: Aqueous Fresh (AQF) extract was prepared to simulate the ethno-medicinal use of CN, and reduced cell viability of MCF-7 cells with IC50 = 1.71 mg/mL. Some CN extracts have the ability to inhibit the proliferation of four different cancer cell lines after a 24 hour treatment. Annexin V assay results shows that acetone extracts of CN induced increments in percentage of apoptotic cell death. However, flow cytometry results show that cancer cell cycle profile were not affected. Similarly, immunoblotting results also indicate that microtubule dynamics in MCF-7 cells were not altered. However, the aqueous extract, prepared to simulate the current ethnomedicinal use of CN leaves in cancer treatment, did not significantly inhibit cancer cell proliferation with IC50 = 1.71 mg/mL. Conclusions: This study was the first to show that microtubules in cancer cells remain dynamic after treatment with CN extracts, effectively ruling interference of microtubule dynamics as the mode of cell death. AMD extract showed the highest effects MCF-7 cell proliferation.

Nuclear expression of E2F4 induces cell death via multiple pathways in normal human intestinal epithelial crypt cells but not in colon cancer cells

2007 ◽  
Vol 293 (4) ◽  
pp. G758-G772 ◽  
Author(s):  
Hugo Garneau ◽  
Laetitia Alvarez ◽  
Marie-Christine Paquin ◽  
Carine Lussier ◽  
Claudine Rancourt ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Death ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Colon Cancer Cells ◽  
Normal Human ◽  
Crypt Cells

E2F transcription factors control cell cycle progression. The localization of E2F4 in intestinal epithelial cells is cell cycle dependent, being cytoplasmic in quiescent differentiated cells but nuclear in proliferative cells. However, whether nuclear translocation of E2F4 alone is sufficient to trigger intestinal epithelial cell proliferation remains to be established. Adenoviruses expressing fusion proteins between green fluorescent protein (GFP) and wild-type (wt)E2F4 or GFP and nuclear localization signal (NLS)-tagged E2F4 were used to infect normal human intestinal epithelial crypt cells (HIEC). In contrast to expression of wtE2F4, persistent expression of E2F4 into the nucleus of HIEC triggered phosphatidylserine exposure, cytoplasmic shrinkage, zeiosis, formation of apoptotic bodies, and activation of caspase 9 and caspase 3. Inhibition of caspase activities by zVAD-fmk partially inhibited cell death induced by E2F4-NLS. An induction of p53, phosphorylated Ser15-p53, PUMA, FAS, BAX, RIP, and phosphorylated JNK1 was also observed in HIEC expressing E2F4-NLS compared with wtE2F4-expressing cells. E2F1 and p14ARF expression remained unaltered. Downregulation of p53 expression by RNA interference attenuated cell death induced by E2F4-NLS. By contrast, the level of cell death was negligible in colon cancer cells despite the strong expression of E2F4 into the nucleus. In conclusion, deregulated nuclear E2F4 expression induces apoptosis via multiple pathways in normal intestinal epithelial cells but not in colon cancer cells. Hence, mutations that deregulate E2F4 localization may provide an initial proliferative advantage but at the same time accelerate cell death. However, intestinal cells acquiring mutations (e.g., p53, Bax loci, etc.) may escape apoptosis, thereby revealing the full mitogenic potential of the E2F4 transcription factor.

scholarly journals Transcriptional network constituted of CBP, Ku70, NOX2, and BAX prevents the cell death of necrosis, paraptosis, and apoptosis in human melanoma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Liang Ding ◽  
Yalei Wen ◽  
Xin Zhang ◽  
Fang Zhao ◽  
Kenao Lv ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Human Melanoma ◽  
Transcriptional Network ◽  
Multiple Roles ◽  
Creb Binding Protein ◽  
Cycle Arrest ◽  
Intracellular Ros ◽  
High Level

AbstractCREB-binding protein (CBP) is an acetyltransferase known to play multiple roles in the transcriptions of genes involving oxidative metabolism, cell cycle, DNA damage checkpoints, and cell death. In this study, CBP was found to positively regulate the expression of Ku70, and both CBP and Ku70 were found to negatively regulate the expression of NOX2, therefore, mitigating the intracellular ROS in human melanoma. Knocking down CBP or Ku70 induced necrotic and paraptotic cell death as indicated by high-level intracellular ROS, cytoplasmic vacuolization, and cell cycle arrest in the S phase. In addition, chromosomal condensations were also observed in the cells proceeding necrotic and paraptotic cell death, which was found to be related to the BAX-associated intrinsic pathway of apoptotic cell death, when Ku70 was decreased either by CBP depletion or by Ku70 depletion directly. Our results, therefore, supported the idea that CBP, Ku70, BAX, and NOX2 have formed a transcriptional network in the prevention of cell death of necrosis, paraptosis, and apoptosis in human melanoma.

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