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

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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Natural compound catechol induces DNA damage, apoptosis, and G1 cell cycle arrest in breast cancer cells

Phytotherapy Research ◽

10.1002/ptr.6970 ◽

2020 ◽

Author(s):

Cijo George Vazhappilly ◽

Rawad Hodeify ◽

Shoib Sarwar Siddiqui ◽

Amina Jamal Laham ◽

Varsha Menon ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Dna Damage ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Natural Compound ◽

Cycle Arrest ◽

G1 Cell Cycle Arrest

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Potential Antitumor Effects of 6-Gingerol in p53-Dependent Mitochondrial Apoptosis and Inhibition of Tumor Sphere Formation in Breast Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22094660 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4660

Author(s):

Nipin Sp ◽

Dong Young Kang ◽

Jin-Moo Lee ◽

Se Won Bae ◽

Kyoung-Jin Jang

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Dna Damage ◽

Side Effects ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Mitochondrial Apoptosis ◽

Cycle Arrest ◽

P53 Activation

Hormone-specific anticancer drugs for breast cancer treatment can cause serious side effects. Thus, treatment with natural compounds has been considered a better approach as this minimizes side effects and has multiple targets. 6-Gingerol is an active polyphenol in ginger with various modalities, including anticancer activity, although its mechanism of action remains unknown. Increases in the level of reactive oxygen species (ROS) can lead to DNA damage and the induction of DNA damage response (DDR) mechanism, leading to cell cycle arrest apoptosis and tumorsphere suppression. Epidermal growth factor receptor (EGFR) promotes tumor growth by stimulating signaling of downstream targets that in turn activates tumor protein 53 (p53) to promote apoptosis. Here we assessed the effect of 6-gingerol treatment on MDA-MB-231 and MCF-7 breast cancer cell lines. 6-Gingerol induced cellular and mitochondrial ROS that elevated DDR through ataxia-telangiectasia mutated and p53 activation. 6-Gingerol also induced G0/G1 cell cycle arrest and mitochondrial apoptosis by mediating the BAX/BCL-2 ratio and release of cytochrome c. It also exhibited a suppression ability of tumorsphere formation in breast cancer cells. EGFR/Src/STAT3 signaling was also determined to be responsible for p53 activation and that 6-gingerol induced p53-dependent intrinsic apoptosis in breast cancer cells. Therefore, 6-gingerol may be used as a candidate drug against hormone-dependent breast cancer cells.

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Bryonia�dioica aqueous extract induces apoptosis and G2/M cell cycle arrest in MDA‑MB 231 breast cancer cells

Molecular Medicine Reports ◽

10.3892/mmr.2019.10220 ◽

2019 ◽

Cited By ~ 1

Author(s):

Bachir Benarba ◽

Almahy Elmallah ◽

Atanasio Pandiella

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Aqueous Extract ◽

Breast Cancer Cells ◽

M Cell ◽

Bryonia Dioica ◽

Cycle Arrest

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Exploring a Link Between NF-kappaB and G2/M Cell Cycle Arrest in Breast Cancer Cells

10.21236/ada425730 ◽

2004 ◽

Author(s):

Shelly M. Davis

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Breast Cancer Cells ◽

M Cell ◽

Cycle Arrest ◽

Nf Kappab

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Exploring a Link Between NF-KB and G2/M Cell Cycle Arrest in Breast Cancer Cells

10.21236/ada436875 ◽

2005 ◽

Author(s):

Shelly M. Davis ◽

Shigeki Miyamoto

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Breast Cancer Cells ◽

M Cell ◽

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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