Clove Buds Affect MCF-7 Breast Cancer Cell Stress/Survival Pathways and Induce Oxidative Stress, DNA Damage, Cell Cycle Arrest, and Apoptosis

Background: As a member of serine/threonine-protein kinase, Polo‐like kinase 1 (PLK1) plays crucial roles during mitosis and also contributes to DNA damage response and repair. PLK1 is aberrantly expressed in many types of tumor cells and increased levels of PLK1 is closely related to tumorigenesis and poor clinical outcomes. Therefore, PLK1 is accepted as one of the potential targets for the discovery of novel anticancer agents. The objective of this study was to assess the cytotoxic effects of a novel PLK1 inhibitor, RO3280, against MCF-7, human breast cancer cells; HepG2, human hepatocellular carcinoma cells; and PC3, human prostate cancer cells, as well as non-cancerous L929 fibroblast cells. Methods: Antiproliferative activity of RO3280 was examined using the XTT assay. Flow cytometry assay was performed to evaluate cell cycle distribution, apoptosis, multicaspase activity, mitochondrial membrane potential, and DNA damage response. We also examined apoptosis with fluorescence imaging studies. Results: According to the results of XTT assay, although RO3280 displayed potent cytotoxicity in all treated cancer cells, the most sensitive cell line was identified as MCF-7 cells that were selected for further studies. The compound induced a cell cycle arrest in MCF-7 cells at G2/M phase and significantly induced apoptosis, multicaspase activity, DNA damage response, and decreased mitochondrial membrane potential of MCF-7 cells. Conclusion: Overall, RO3280 induces anticancer effects promoted mainly by DNA damage, cell cycle arrest, and apoptosis in breast cancer cells. Further studies are needed to assess its usability as an anticancer agent with specific cancer types.

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Metformin Induces Apoptosis and Cell Cycle Arrest Mediated by Oxidative Stress, AMPK and FOXO3a in MCF-7 Breast Cancer Cells

PLoS ONE ◽

10.1371/journal.pone.0098207 ◽

2014 ◽

Vol 9 (5) ◽

pp. e98207 ◽

Cited By ~ 140

Author(s):

Eveline A. I. F. Queiroz ◽

Stephanie Puukila ◽

Rosangela Eichler ◽

Sandra C. Sampaio ◽

Heidi L. Forsyth ◽

...

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cycle Arrest ◽

Mcf 7

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An Aqueous Extract of Fagonia cretica Induces DNA Damage, Cell Cycle Arrest and Apoptosis in Breast Cancer Cells via FOXO3a and p53 Expression

PLoS ONE ◽

10.1371/journal.pone.0040152 ◽

2012 ◽

Vol 7 (6) ◽

pp. e40152 ◽

Cited By ~ 49

Author(s):

Matt Lam ◽

Amtul R. Carmichael ◽

Helen R. Griffiths

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Dna Damage ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Aqueous Extract ◽

Breast Cancer Cells ◽

P53 Expression ◽

Damage Cell ◽

Cycle Arrest

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Ecotoxicological assessment of cobalt using Hydra model: ROS, oxidative stress, DNA damage, cell cycle arrest, and apoptosis as mechanisms of toxicity

Environmental Pollution ◽

10.1016/j.envpol.2016.12.042 ◽

2017 ◽

Vol 224 ◽

pp. 54-69 ◽

Cited By ~ 21

Author(s):

Mohammed Zeeshan ◽

Anbazhagan Murugadas ◽

Surendra Ghaskadbi ◽

Babu Rajendran Ramaswamy ◽

Mohammad Abdulkader Akbarsha

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Dna Damage ◽

Cell Cycle Arrest ◽

Ecotoxicological Assessment ◽

Damage Cell ◽

Mechanisms Of Toxicity ◽

Cycle Arrest

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Mutant p53L194F Harboring Luminal-A Breast Cancer Cells Are Refractory to Apoptosis and Cell Cycle Arrest in Response to MortaparibPlus, a Multimodal Small Molecule Inhibitor

Cancers ◽

10.3390/cancers13123043 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3043

Author(s):

Ahmed Elwakeel ◽

Anissa Nofita Sari ◽

Jaspreet Kaur Dhanjal ◽

Hazna Noor Meidinna ◽

Durai Sundar ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Small Molecule ◽

Breast Cancer Cells ◽

Luminal A ◽

Molecular Analyses ◽

Cycle Arrest ◽

Mcf 7

We previously performed a drug screening to identify a potential inhibitor of mortalin–p53 interaction. In four rounds of screenings based on the shift in mortalin immunostaining pattern from perinuclear to pan-cytoplasmic and nuclear enrichment of p53, we had identified MortaparibPlus (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole) as a novel synthetic small molecule. In order to validate its activity and mechanism of action, we recruited Luminal-A breast cancer cells, MCF-7 (p53wild type) and T47D (p53L194F) and performed extensive biochemical and immunocytochemical analyses. Molecular analyses revealed that MortaparibPlus is capable of abrogating mortalin–p53 interaction in both MCF-7 and T47D cells. Intriguingly, upregulation of transcriptional activation function of p53 (as marked by upregulation of the p53 effector gene—p21WAF1—responsible for cell cycle arrest and apoptosis) was recorded only in MortaparibPlus-treated MCF-7 cells. On the other hand, MortaparibPlus-treated T47D cells exhibited hyperactivation of PARP1 (accumulation of PAR polymer and decrease in ATP levels) as a possible non-p53 tumor suppression program. However, these cells did not show full signs of either apoptosis or PAR-Thanatos. Molecular analyses attributed such a response to the inability of MortaparibPlus to disrupt the AIF–mortalin complexes; hence, AIF did not translocate to the nucleus to induce chromatinolysis and DNA degradation. These data suggested that the cancer cells possessing enriched levels of such complexes may not respond to MortaparibPlus. Taken together, we report the multimodal anticancer potential of MortaparibPlus that warrants further attention in laboratory and clinical studies.

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

Cells ◽

10.3390/cells8010008 ◽

2018 ◽

Vol 8 (1) ◽

pp. 8 ◽

Cited By ~ 5

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.

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