scholarly journals Suppression of Tumorigenicity 5 Ameliorates Tumor Characteristics of Invasive Breast Cancer Cells via Integrating ERK/JNK Pathway

2020 ◽  
Author(s):  
Jianghong Cheng ◽  
Mingli Li ◽  
Chi-Meng Tzeng ◽  
Xingchun Gou ◽  
Shuai Chen
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Tumor Suppressor ◽  
Cell Viability ◽  
Cancer Cells ◽  
Invasive Breast Cancer ◽  
Breast Cancer Cells ◽  
Suppressor Gene ◽  
Pathological Stages ◽  
Mcf 7

Abstract Background: Suppression of tumorigenicity 5 (ST5) has been considered as a tumor suppressor gene in HeLa tumor cells. However, there is no report of ST5 expression or function in the progression of breast cancer.Methods: ST5 expression in different subtypes and pathological stages of breast cancer was determined by Oncomine database, Breast Cancer Gene-Expression Miner v4.4 (bc-GenExMiner v4.4) analysis and immunohistochemistry. Cell viability was measured by CCK8 assay and metastatic behavior was assessed using scratch wound model and Transwell. Flow cytometry was employed for cell cycle and apoptosis detection, and methylation-specific PCR (MSP) was used to detect methylation level.Results: ST5 was expressed at low level in different subtypes of breast cancer specimens compared to normal breast and there was a negative association between ST5 status and pathological stages of breast cancer patients. Additionally, ST5 was lower in cases of recurrent and invasive breast cancer than that in non-recurrent and non-invasive patients. In in vitro experiment, ST5 status was also negatively associated with the invasive capability of breast cancer cells, showing lower in MDA-MB-231 and SKBR3 cell lines than that in MCF-7 cells. ST5-downregulation promoted, while ST5-upregulation inhibited the tumour characteristics of MDA-MB-231 cells including cell viability, cell cycle and migration. And exogenous ST5 also elevated, but ST5 depletion limited the proportion of apoptotic cells in MDA-MB-231 cells. However, the alteration of ST5, no matter upregulation or downregulation, had no impact on tumour behaviors of MCF-7 cells. Mechanistically, ST5 protein ablation activated, while ST5-upregulation repressed the activities of phosphorylated JNK and ERK1/2, and subsequently the expression of c-Myc. Of note, low level of ST5 in breast cancer cells was possibly related with the aberrant methylation of ST5 promoter region.Conclusion: Our findings suggest that ST5 potentially acts as a tumor suppressor gene in invasive breast cancer through regulating ERK/JNK signaling pathway and provide a novel insight for breast cancer treatment.

scholarly journals Suppression of Tumorigenicity 5 Ameliorates Tumor Characteristics of Invasive Breast Cancer Cells via ERK/JNK Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianghong Cheng ◽  
Mingli Li ◽  
Chi-Meng Tzeng ◽  
Xingchun Gou ◽  
Shuai Chen
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Tumor Suppressor Gene ◽  
Invasive Breast Cancer ◽  
Breast Cancer Cells ◽  
Suppressor Gene ◽  
And Migration ◽  
Invasive Capability ◽  
Mcf 7

BackgroundSuppression of tumorigenicity 5 (ST5) has been considered as a tumor suppressor gene in HeLa tumor cells. However, its role in the progression of breast cancer remains vague.MethodsOnline database analysis was determined by Oncomine and Breast Cancer Gene-Expression Miner v4.4 (bc-GenExMiner v4.4). Tumor biology behaviors were measured by MTT assay, wound healing model, Transwell and Flow cytometry assays. Methylation-specific PCR (MSP) was employed to detect promoter methylation.ResultsLow level of ST5 was observed in breast cancer specimens, particularly in recurrent, invasive breast cancer cases compared to para-carcinoma tissue or non-invasive breast cancer. The downregulation of ST5 was also proved in MDA-MB-231 and SKBR3 cell lines with a high invasive capability as compared to MCF-7 cell with a low invasive capability. ST5 was negatively associated with pathological stages of breast cancer. ST5-downregulation promoted, while ST5-upregulation inhibited the progression of cell proliferation, cell cycle and migration of MDA-MB-231 cells. Additionally, ST5 knockdown inhibited, whereas ST5 overexpression promoted apoptosis of MDA-MB-231 cells. However, ST5 modification, either upregulation or downregulation, had no significant impact on tumor behaviors of MCF-7 cells. Mechanistically, ST5 protein ablation activated, while ST5-upregulation repressed the activities of phosphorylated ERK1/2 and JNK, and subsequently the expression of c-Myc. PD98059-mediated ERK1/2 inhibition abolished the stimulatory effects of ST5-depletion on ERK1/2/JNK/c-Myc signaling axis, and ST5 depletion-mediated cell over-proliferation and migration. Of note, ST5 reduction in invasive breast cancer cells should implicate in the hypermethylation of ST5 promoter region.ConclusionOur findings suggest that ST5 potentially acts as a tumor suppressor gene in invasive breast cancer through regulating ERK/JNK signaling pathway and provide a novel insight for breast cancer treatment.

scholarly journals DC-SCRIPT is a novel regulator of the tumor suppressor gene CDKN2B and induces cell cycle arrest in ERα-positive breast cancer cells

2015 ◽  
Vol 149 (3) ◽  
pp. 693-703 ◽  
Author(s):  
Marleen Ansems ◽  
Jonas Nørskov Søndergaard ◽  
Anieta M. Sieuwerts ◽  
Maaike W. G. Looman ◽  
Marcel Smid ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Tumor Suppressor ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Tumor Suppressor Gene ◽  
Breast Cancer Cells ◽  
Suppressor Gene ◽  
Cycle Arrest ◽  
Positive Breast Cancer

scholarly journals 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 ◽  
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.

scholarly journals PGV-0 AND PGV-1 INCREASED APOPTOSIS INDUCTION OF DOXORUBICIN ON MCF-7 BREAST CANCER CELLS

2015 ◽  
Vol 12 (2) ◽  
pp. 55-59
Author(s):  
Edy Meiyanto
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agent ◽  
Apoptosis Induction ◽  
Single Treatment ◽  
Cell Cycle Modulation ◽  
Induced Apoptosis ◽  
Mcf 7

As chemotherapeutic backbone for breast cancer therapy, doxorubicin showed various side effects and induced resistancy of breast cancer cells. Development of targeted therapy on breast cancer focused on combinatorial therapy of doxorubicin and molecular targeted agents. PGV-0 and PGV-1, a curcumin analogue showed potency as co-chemotherapeutic agent with doxorubicin. Our previous study of PGV-0 and PGV-1 showed cytotoxic activity in T47D cells. Therefore, the aim of this research is to examine the synergistic effect of PGV-0, PGV-1 on the cytotoxic activity of doxorubicin through cell cycle modulation and apoptotic induction on MCF-7 breast cancer cell lines. The cytotoxic assay of PGV-0, PGV-1, doxorubicin, and their combination were carried out by using MTT assay. Cell cycle distribution and apoptosis were determined by flowcytometer FACS-Calibur and the flowcytometry data was analyzed using Cell Quest program. Single treatment of PGV-0, PGV-1 and doxorubicin showed cytotoxic effect on MCF-7 with cell viability IC50 value 50 µM, 6 µM and 350 nM respectively. Single treatment of Doxorubicin 175 nM induced G2/M arrest. Single treatment of PGV-0 5 µM induced G2/M arrest while in higher dose 12.5  µM, PGV-0 induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 5 µM induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 12.5 µM also increased apoptosis induction. Single treatment of PGV-1 0.6 µM induced G1 arrest while in higher dose 1.5  µM, PGV-1 induced apoptosis. Combination of doxorubicin 175 nM and PGV-1 0.6 µM induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 1.5 µM also increased apoptosis induction. PGV-0 and PGV-1 are potential to be delevoped as co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle modulation, but the molecular mechanism need to be explored detail.  Key words: PGV-0, PGV-1, doxorubicin, co-chemotherapy, breast cancer, cell cycle arrest, apoptosis

scholarly journals Induction of PDCD4 tumor suppressor gene expression by RAR agonists, antiestrogen and HER-2/neu antagonist in breast cancer cells. Evidence for a role in apoptosis

Oncogene ◽  
2004 ◽  
Vol 23 (49) ◽  
pp. 8135-8145 ◽  
Author(s):  
Olubunmi Afonja ◽  
Dominique Juste ◽  
Sharmistha Das ◽  
Sachiko Matsuhashi ◽  
Herbert H Samuels
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Tumor Suppressor Gene ◽  
Breast Cancer Cells ◽  
Suppressor Gene ◽  
Her 2

Ganoderma lucidum Extract Induces G1 Cell Cycle Arrest, and Apoptosis in Human Breast Cancer Cells

2012 ◽  
Vol 40 (03) ◽  
pp. 631-642 ◽  
Author(s):  
Guosheng Wu ◽  
Zhengming Qian ◽  
Jiajie Guo ◽  
Dejun Hu ◽  
Jiaolin Bao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest ◽  
Mcf 7

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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