scholarly journals A New Highlight of Ephedra alata Decne Properties as Potential Adjuvant in Combination with Cisplatin to Induce Cell Death of 4T1 Breast Cancer Cells In Vitro and In Vivo

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 362 ◽  
Author(s):  
Fairouz Sioud ◽  
Souheila Amor ◽  
Imène ben Toumia ◽  
Aida Lahmar ◽  
Virginie Aires ◽  
...  

Despite major advances in the last 10 years, whether in terms of prevention or treatment, the 5 year survival rate remains relatively low for a large number of cancers. These therapeutic failures can be the consequence of several factors associated with the cellular modifications or with the host by itself, especially for some anticancer drugs such as cisplatin, which induces a nephrotoxicity. In the strategy of research for active molecules capable both of exerting a protective action against the deleterious effects of cisplatin and exerting a chemosensitizing action with regard to cancer cells, we tested the potential effects of Ephedra alata Decne extract (E.A.) rich in polyphenolic compounds towards a 4T1 breast cancer model in vitro and in vivo. We showed that E.A. extract inhibited cell viability of 4T1 breast cancer cells and induced apoptosis in a caspase-dependent manner, which involved intrinsic pathways. Very interestingly, we observed a synergic antiproliferative and pro-apoptotic action with cisplatin. These events were associated with a strong decrease of breast tumor growth in mice treated with an E.A./cisplatin combination and simultaneously with a decrease of hepato- and nephrotoxicities of cisplatin.

2009 ◽  
Vol 16 (4) ◽  
pp. 1185-1195 ◽  
Author(s):  
Céline Van Themsche ◽  
Sophie Parent ◽  
Valérie Leblanc ◽  
Caroline Descôteaux ◽  
Anne-Marie Simard ◽  
...  

We have previously reported the synthesis of VP-128, a new 17β-oestradiol (E2)-linked platinum(II) hybrid with high affinity for oestrogen receptor α (ERα). In the present study, we have investigated the anti-tumour activity of VP-128 towards breast cancer cells in vitro and in vivo. We used human ERα-positive (MCF-7) and -negative (MDA-MB-468) cells as a model for treatment with increasing doses of VP-128, cisplatin or E2 in vitro and for xenograft experiments in nude mice in vivo. Compared with cisplatin, VP-128 showed markedly improved in vitro and in vivo anti-tumour activity towards ERα-positive MCF-7 breast cancer cells, without increased systemic toxicity. In these caspase-3-deficient cells, treatment with VP-128 overcame weak cellular sensitivity to cisplatin in vitro and in vivo. In these cells, only the hybrid induced apoptosis in an ERα-dependent manner, inactivated both X-linked inhibitor of apoptosis protein and Akt, and induced selective nuclear accumulation of ERα and the expression of ER-regulated genes c-myc and tff1, which was blocked by ERα-specific antagonist ICI 282 780. In the case of ERα-negative MDA-MB-468 cells, VP-128, but not cisplatin, induced nuclear accumulation of apoptosis-inducing factor and inhibited c-myc expression. However, VP-128 did not show enhanced in vivo anti-tumour activity compared with cisplatin. These results reveal two different modes of action for VP-128 in ERα-positive and -negative breast cancer cells, and highlight the promising therapeutic value of this unique E2-platinum hybrid for selective targeting of hormone-dependent cancers.


2018 ◽  
Vol 50 (6) ◽  
pp. 2108-2123 ◽  
Author(s):  
Ruifang Gao ◽  
Yanhua Liu ◽  
Dan Li ◽  
Jing Xun ◽  
Wei Zhou ◽  
...  

Background/Aims: The bi-functional enzyme 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase-4 (PFKFB4) is highly expressed in many types of cancer and its requirement for tumor survival has been demonstrated in glioma, lung, and prostate cancers. However, whether PFKFB4 plays a role in the tumor metastasis remains uncertain. This study explores the role of PFKFB4 in tumor metastasis and its underlying mechanisms in breast cancer cells. Methods: The expression of PFKFB4 was first analyzed using the Cancer Genome Atlas (TCGA) dataset, and confirmed by immunohistochemical staining of tissue microarray and breast cancer tissues from patient samples. Gain- and loss-of- function approaches were used to investigate the effects of PFKFB4 on breast cancer cell migration in vitro. Orthotopic xenograft model and experimental metastasis model were used to assess the effects of PFKFB4 on breast cancer cell metastasis in vivo. ELISA and immunofluorescence staining were used to examine HA production. Quantitative RT-PCR and western blotting were used to explore the mRNA and protein levels of HAS2, respectively. Results: We found that PFKFB4 enhances the migration/invasiveness of breast cancer cells in vitro as well as in vivo. Notably, the effects of PFKFB4 on migration are mediated by induction of HAS2 expression and HA production. Moreover, PFKFB4-induced HAS2 up-regulation depends upon the activation of p38 signaling. Conclusion: PFKFB4 promotes the metastasis of breast cancer cells via induction of HAS2 expression and HA production in a p38-dependent manner. Therefore, the PFKFB4/p38/HAS2 signaling pathway may serve as a potential therapeutic target for metastatic breast cancer.


2021 ◽  
Author(s):  
Xiuping Kuang ◽  
Yingnan Jiang ◽  
Jiwei Huang ◽  
Yongzhi Guo ◽  
weixi Li

Abstract Background Indirubin, isolated from Indigo Naturals, is reported to have the inhibitory activity of MCF-7 human breast cancer cells in vitro. However, studies on its anti-breast cancer activity in vivo and underlying mechanism are insufficient. We explored whether indirubin could trigger ferroptosis of breast cancer cells to exert anti-tumor activity. Methods Bioinformatical analysis was performed to detected the expression of prostaglandin-endoperoxide synthase 2 (Ptgs2) in breast cancer tissues Ptgs2-related prognosis for patients with breast cancer. Growth of 4T1 cells was assessed using wound healing assay and MTT assay. The levels of 4-HNE, GPX4, PTGS2 and GSK-3β proteins were detected by Western blot, and the mRNA of Ptgs2 was tested by qPCR. The GSH and MDA were determined by commercial kits. Molecular docking was employed to study interaction between indirubin and GSK-3β. An 4T1 murine breast cancer was adopted to evaluate the in vivo antitumor activity of indirubin. Results Indirubin promoted ferroptosis of 4T1 breast cancer cells with deplete of GSH, increased MDA and 4-HNE level, as well as decreased GPX4 expression. Indirubin suppressed the growth of 4T1 breast tumor in vivo. Mechanism study showed indirubin up regulated Ptgs2 expression by promoting phosphorylation (Ser 9) of GSK-3β. Conclusions Indirubin suppresses 4T1 murine breast cancer in vitro and in vivo by induction of ferroptosis and up-regulation of Ptgs2.


RSC Advances ◽  
2017 ◽  
Vol 7 (57) ◽  
pp. 36185-36192 ◽  
Author(s):  
Nursyamirah Abd Razak ◽  
M. Nadeem Akhtar ◽  
Nadiah Abu ◽  
Wan Yong Ho ◽  
Sheau Wei Tan ◽  
...  

BHMC possessedin vitroandin vivoantitumor effect on 4T1 triple negative breast cancer cells.


Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2670 ◽  
Author(s):  
Noraini Nordin ◽  
Swee Keong Yeap ◽  
Heshu Sulaiman Rahman ◽  
Nur Rizi Zamberi ◽  
Nurul Elyani Mohamad ◽  
...  

Cancer nano-therapy has been progressing rapidly with the introduction of many novel drug delivery systems. The previous study has reported on the in vitro cytotoxicity of citral-loaded nanostructured lipid carrier (NLC-Citral) on MDA-MB-231 cells and some preliminary in vivo antitumor effects on 4T1 breast cancer cells challenged mice. However, the in vivo apoptosis induction and anti-metastatic effects of NLC-Citral have yet to be reported. In this study, the in vitro cytotoxic, anti-migration, and anti-invasion effects of NLC-Citral were tested on 4T1 breast cancer cells. In addition, the in vivo antitumor effects of oral delivery of NLC-Citral was also evaluated on BALB/c mice induced with 4T1 cells. In vitro cytotoxicity results showed that NLC-Citral and citral gave similar IC50 values on 4T1 cells. However, wound healing, migration, and invasion assays reflected better in vitro anti-metastasis potential for NLC-Citral than citral alone. Results from the in vivo study indicated that both NLC-Citral and citral have anti-tumor and anti-metastasis effects, whereby the NLC-Citral showed better efficacy than citral in all experiments. Also, the delay of tumor progression was through the suppression of the c-myc gene expression and induction of apoptosis in the tumor. In addition, the inhibition of metastasis of 4T1 cells to lung and bone marrow by the NLC-Citral and citral treatments was correlated with the downregulation of metastasis-related genes expression including MMP-9, ICAM, iNOS, and NF-kB and the angiogenesis-related proteins including G-CSF alpha, Eotaxin, bFGF, VEGF, IL-1alpha, and M-CSF in the tumor. Moreover, NLC-Citral showed greater downregulation of MMP-9, iNOS, ICAM, Eotaxin, bFGF, VEGF, and M-CSF than citral treatment in the 4T1-challenged mice, which may contribute to the better anti-metastatic effect of the encapsulated citral. This study suggests that NLC is a potential and effective delivery system for citral to target triple-negative breast cancer.


2018 ◽  
Vol 73 (3-4) ◽  
pp. 137-145 ◽  
Author(s):  
Cigdem Karaaslan ◽  
Filiz Bakar ◽  
Hakan Goker

AbstractBreast cancer is the most endemic cause of cancer among women in both developed and developing countries. Benzimidazole derivatives exemplify one of the chemical classes that show strong cytotoxic activity especially against breast cancer cells (MCF-7). Aromatic amidine derivatives are known as a group of DNA interactive compounds that bind minor groove of the genome, especially A-T base pairs, and show significant in vitro and in vivo toxicity toward cancer cells. In light of these studies, some new mono/dicationic amidino benzimidazole derivatives were synthesized and evaluated for cytotoxic activity on cultured MCF-7 breast cancer cells. Some of these compounds have strongly inhibited MCF-7 cell viability in a dose-dependent manner compared with clinically used reference compounds, imatinib mesylate and docetaxel. Among them, 4-[(5(6)-bromo-1H-benzimidazole-2-yl)amino]benzene-1-carboxamidine (30) showed the best inhibitory activity with IC50value of 4.6 nM.


2019 ◽  
Vol 63 (0) ◽  
Author(s):  
Nurul Elyani Mohamad ◽  
Swee Keong Yeap ◽  
Nadiah Abu ◽  
Kian Lam Lim ◽  
Nur Rizi Zamberi ◽  
...  

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