Oxocrebanine: A Novel Dual Topoisomerase inhibitor, Suppressed the Proliferation of Breast Cancer Cells MCF-7 by Inducing DNA Damage and Mitotic Arrest

Abstract Multicellular tumor spheroids (MCTSs) constitute a three-dimensional culture system that recapitulates the in vivo tumor microenvironment. Tumor cells cultured as MCTSs present antineoplastic resistance due to the effect of microenvironmental signals acting upon them. In this work, we evaluated the biological function of a new microenvironment-regulated long non-coding RNA, lncMat2B, in breast cancer. In MCTSs, the expression of lncMat2B presented an increase and a zonal heterogeneity, as it was expressed principally in quiescent cells of hypoxic regions of the MCTSs. As expected, functional assays supported the role of severe hypoxia in the regulation of lncMat2B. Moreover, gain- and loss-of-function assays using a transcriptional silencing CRISPR/Cas9 system and gBlock revealed that lncMAT2B regulates the tumor-initiating phenotype. Interestingly, lncMat2B is overexpressed in a cisplatin-resistant MCF-7 cell line, and its ectopic expression in wild type MCF-7 cells increased survival to cisplatin exposure by reducing DNA damage and reactive oxygen species accumulation. lncMAT2B is a possible link between severe hypoxia, tumor-initiating phenotype and drug resistance in breast cancer cells.

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Induction and processing of complex DNA damage in human breast cancer cells MCF-7 and nonmalignant MCF-10A cells

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2007.10.045 ◽

2008 ◽

Vol 44 (4) ◽

pp. 558-569 ◽

Cited By ~ 42

Author(s):

Dave C. Francisco ◽

Prakash Peddi ◽

Jessica M. Hair ◽

Brittany A. Flood ◽

Angela M. Cecil ◽

...

Keyword(s):

Breast Cancer ◽

Dna Damage ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Mcf 7

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Resveratrol‐induced DNA Damage on MCF‐7 Breast Cancer Cells Through NER Pathway

The FASEB Journal ◽

10.1096/fasebj.2018.32.1_supplement.647.8 ◽

2018 ◽

Vol 32 (S1) ◽

Author(s):

Luis Angel Padilla ◽

Ralphdy Angel Vergne ◽

Carmen Ortiz ◽

Lenin Godoy ◽

Jarline Encarnacion ◽

...

Keyword(s):

Breast Cancer ◽

Dna Damage ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Mcf 7

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RO3280: A Novel PLK1 Inhibitor, Suppressed the Proliferation of MCF-7 Breast Cancer Cells Through the Induction of Cell Cycle Arrest at G2/M Point

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190618162828 ◽

2019 ◽

Vol 19 (15) ◽

pp. 1846-1854 ◽

Cited By ~ 4

Author(s):

Mustafa Ergul ◽

Filiz Bakar-Ates

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Dna Damage ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Dna Damage Response ◽

Breast Cancer Cells ◽

Cycle Arrest ◽

Damage Response ◽

Mcf 7

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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Cucurbita ficifolia Fruit Extract Induces Tp53/Caspase-Mediated Apoptosis in MCF-7 Breast Cancer Cells

BioMed Research International ◽

10.1155/2020/3712536 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Ghedeir M. Alshammari ◽

Aristatile Balakrishnan ◽

Ali A. Alshatwi ◽

Abdulrahman Al-Khalifa

Keyword(s):

Breast Cancer ◽

Dna Damage ◽

Cell Death ◽

Programmed Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Time Dependent ◽

Fruit Extract ◽

Cucurbita Ficifolia ◽

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The second most biggest cancer worldwide is breast cancer. There is an increasing need for safer, effective, and affordable drug candidates from natural sources to treat breast cancer. In the present investigation, the anticancer effect of Cucurbita ficifolia Bouché (C. ficifolia) fruit extract was tested on the human breast cancer cells such as MCF-7. The cells were exposed with different doses of C. ficifolia, for the assessment of IC50 concentrations on the MCF-7 cell lines for 24 hs. The effect of C. ficifolia fruit extract on morphological and apoptotic changes were evaluated by specific fluorescence staining techniques and real-time PCR in a time-dependent manner for 24 hs and 48 hs. The IC50 value for C. ficifolia fruit extract was found to be 90 μg/mL. Morphological alteration and apoptotic distinctiveness aspect like chromatin condensation and nuclear fragmentation were noticed in C. ficifolia extract exposed breast cancer cells. Further, we observed that C. ficifolia extract-induced programmed cell death in the MCF-7 cells were mediated with the elevated expression of the tumor suppressor gene such as p53 and apoptotic markers such as caspase-8, caspase-9, caspase-3, fatty acid synthase (FAS), Fas-associated protein with death domain (FADD), Bcl-2 homologous antagonist/killer (BAK), and Bcl-2-associated X protein (BAX). These observations established that C. ficifolia significantly concealed the cell division and provoked p53/caspase-mediated programmed cell death. Further, we noticed that this cell death in MCF-7 cells is concentration and time dependent. As evaluated through the comet assay, C. ficifolia induced DNA damage; further upon increasing the duration of the treatment, the DNA damage was higher than before. Thus, our study concludes that C. ficifolia could serve as an effective anticancer agent through vital gene modulation.

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