P53-mediated cell cycle arrest and apoptosis through a caspase-3-independent, but caspase-9-dependent pathway in oridonin-treated MCF-7 human breast cancer cells

Ganoderma lucidum (Fr.) Karst is a traditional Chinese herb that has been widely used for centuries to treat various diseases including cancer. Herein, an ethanol-soluble and acidic component (ESAC), which mainly contains triterpenes, was prepared from G. lucidum and its anti-tumor effects in vitro were tested on human breast cancer cells. Our results showed that ESAC reduced the cell viability of MCF-7 and MDA-MB-231 cells in a concentration-dependent manner with IC50 of about 100 μg/mL and 60 μg/mL, respectively. DNA damage was detected by Comet assay and the increased expression of γ-H2AX after ESAC treatment was determined in MCF-7 cells. Moreover, ESAC effectively mediated G1 cell cycle arrest in both concentration- and time-dependent manners and induced apoptosis as determined by Hoechst staining, DNA fragment assay and Western blot analysis in MCF-7 cells. In conclusion, ESAC exerts anti-proliferation effects by inducing DNA damage, G1 cell cycle arrest and apoptosis in human breast cancer cells.

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Insulin-like Growth Factor Binding Protein-3 Induces G1 Cell Cycle Arrest with Inhibition of Cyclin-dependent Kinase 2 and 4 in MCF-7 Human Breast Cancer Cells

Hormone and Metabolic Research ◽

10.1055/s-0029-1243190 ◽

2009 ◽

Vol 42 (03) ◽

pp. 165-172 ◽

Cited By ~ 15

Author(s):

H.-S. Kim ◽

W. J. Lee ◽

S. W. Lee ◽

H.-W. Chae ◽

D. H. Kim ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Cyclin Dependent Kinase ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Cycle Arrest ◽

G1 Cell Cycle Arrest ◽

Mcf 7

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Resveratrol-induced Apoptosis in Human Breast Cancer Cells Is Mediated Primarily through the Caspase-3-dependent Pathway

Archives of Medical Research ◽

10.1016/j.arcmed.2007.09.003 ◽

2008 ◽

Vol 39 (2) ◽

pp. 162-168 ◽

Cited By ~ 41

Author(s):

Moussa Alkhalaf ◽

Abdulla El-Mowafy ◽

Waleed Renno ◽

Ousama Rachid ◽

Ahmed Ali ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Caspase 3 ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Induced Apoptosis ◽

Dependent Pathway

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Proapoptotic and Antiproliferative Effects ofThymus caramanicuson Human Breast Cancer Cell Line (MCF-7) and Its Interaction with Anticancer Drug Vincristine

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/893247 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 9

Author(s):

Saeed Esmaeili-Mahani ◽

Farzaneh Falahi ◽

Mohammad Mehdi Yaghoobi

Keyword(s):

Breast Cancer ◽

Cyclin D1 ◽

Cancer Cells ◽

Anticancer Drug ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Caspase 3 ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Mcf 7

Thymus caramanicus Jalasis one of the species of thymus that grows in the wild in different regions of Iran. Traditionally, leaves of this plant are used in the treatment of diabetes, arthritis, and cancerous situation. Therefore, the present study was designed to investigate the selective cytotoxic and antiproliferative properties ofThymus caramanicusextract (TCE). MCF-7 human breast cancer cells were used in this study. Cytotoxicity of the extract was determined using MTT and neutral red assays. Biochemical markers of apoptosis (caspase 3, Bax, and Bcl-2) and cell proliferation (cyclin D1) were evaluated by immunoblotting. Vincristine was used as anticancer control drug in extract combination therapy. The data showed that incubation of cells with TCE (200 and 250 μg/mL) significantly increased cell damage, activated caspase 3 and Bax/Bcl2 ratio. In addition, cyclin D1 was significantly decreased in TCE-treated cells. Furthermore, concomitant treatment of cells with extract and anticancer drug produced a significant cytotoxic effect as compared to extract or drugs alone. In conclusion, thymus extract has a potential proapoptotic/antiproliferative property against human breast cancer cells and its combination with chemotherapeutic agent vincristine may induce cell death effectively and be a potent modality to treat this type of cancer.

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Flavonoids, bioactive components of propolis, exhibit cytotoxic activity and induce cell cycle arrest and apoptosis in human breast cancer cells MDA-MB-231 and MCF-7 – a comparative study

Cellular and Molecular Biology ◽

10.14715/cmb/2018.64.8.1 ◽

2018 ◽

Vol 64 (8) ◽

pp. 1 ◽

Cited By ~ 14

Author(s):

Agata Kabała-Dzik ◽

Anna Rzepecka-Stojko ◽

Robert Kubina ◽

Marcello Iriti ◽

Robert D Wojtyczka ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Bioactive Components ◽

Human Breast ◽

Induce Cell Cycle Arrest ◽

Cycle Arrest ◽

Mcf 7

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VALD-3, a Schiff base ligand synthesized from o-vanillin derivatives, induces cell cycle arrest and apoptosis in breast cancer cells by inhibiting the Wnt/β-catenin pathway

10.21203/rs.3.rs-31504/v2 ◽

2020 ◽

Author(s):

Hongling Li ◽

Chunyan Dang ◽

Xiaohui Tai ◽

Li Xue ◽

Yuna Meng ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Cycle Arrest ◽

Apoptotic Proteins ◽

Mcf 7

Abstract Background: Schiff base compounds and their metal complexes have become important synthetic organic drugs due to their extensive biological activities, which include anticancer, antibacterial and antiviral effects. In this study, we investigated the cytotoxic and apoptotic effects of VALD-3, a Schiff base ligand synthesized from o-vanillin derivatives, on human breast cancer cells and the possible underlying mechanisms.Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-test was used to observe the proliferation of human breast cancer MCF-7 and MDA-MB-231 cells induced on VALD-3. The effects of VALD-3 on the cell cycle were analyzed in MCF-7 and MDA-MB-231 cells by PI single staining. Hoechst 33258 staining was performed to determine if VALD-3 induced apoptosis of MCF-7 and MDA-MB-231 cells and Annexin V/PI staining was performed to quantify the percentages of apoptosis. The expression of pro-apoptotic proteins and anti-apoptotic proteins in MCF-7 and MDA-MB-231 cells was investigated by Western blotting. Wnt/β-catenin signaling pathways were also examined. The antitumor activity and survival analysis of VALD-3 in vivo was determined by the nude mice xenograft assay.Results: Flow cytometry analysis showed that VALD-3 triggered cell cycle arrest and induced apoptosis of breast cancer cells. Western blot analysis revealed that VALD-3 upregulated pro-apoptotic proteins (Bad and Bax), downregulated anti-apoptotic proteins (Bcl-2, Bcl-xl, survivin and XIAP) and increased the expression of cleaved caspase-3, cleaved caspase-8, Cyto-c and cleaved PARP. VALD-3 also regulated the Wnt/β-catenin signaling pathway in breast cancer cells, inhibiting the activation of downstream molecules. By xenografting human breast cancer cells into nude mice, we found that VALD-3 significantly suppressed tumor cell growth while showing low toxicity against major organs. In addition, survival analysis results showed that VALD-3 can significantly prolong the survival time of mice (P=0.036).Conclusion: This study is the first to show that VALD-3 induces apoptosis and cell cycle arrest in human breast cancer cells by suppressing Wnt/β-catenin signaling, indicating that it could be a potential drug for the treatment of breast cancer.

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