Antitumor and Anti-Metastatic Effects of Citral-Loaded Nanostructured Lipid Carrier in 4T1-Induced Breast Cancer Mouse Model

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.

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In vitro evaluation of estrogenic, antiestrogenic and antitumor effects of amentoflavone

Human & Experimental Toxicology ◽

10.1177/0960327121999454 ◽

2021 ◽

pp. 096032712199945

Author(s):

AT Aliyev ◽

S Ozcan-Sezer ◽

A Akdemir ◽

H Gurer-Orhan

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Antitumor Effects ◽

Antiestrogenic Activity ◽

Er Positive ◽

In Vivo Effects ◽

Mcf 7

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects.

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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 ◽

10.3390/cells9020362 ◽

2020 ◽

Vol 9 (2) ◽

pp. 362 ◽

Cited By ~ 6

Author(s):

Fairouz Sioud ◽

Souheila Amor ◽

Imène ben Toumia ◽

Aida Lahmar ◽

Virginie Aires ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Protective Action ◽

Dependent Manner ◽

4T1 Breast Cancer ◽

Induced Apoptosis ◽

Cellular Modifications

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.

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In vitro and In vivo Antitumor Effects of Deoxyelephantopin on Human Breast Cancer Cells

Planta Medica ◽

10.1055/s-0031-1282858 ◽

2011 ◽

Vol 77 (12) ◽

Author(s):

K Aravindaram ◽

Y Chen ◽

P Wang ◽

C Lan ◽

C Huang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Antitumor Effects

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Iron Oxide Nanoparticles as Carriers for DOX and Magnetic Hyperthermia after Intratumoral Application into Breast Cancer in Mice: Impact and Future Perspectives

Nanomaterials ◽

10.3390/nano10061016 ◽

2020 ◽

Vol 10 (6) ◽

pp. 1016 ◽

Cited By ~ 2

Author(s):

Susann Piehler ◽

Heidi Dähring ◽

Julia Grandke ◽

Julia Göring ◽

Pierre Couleaud ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Tumor Volume ◽

Tumor Regression ◽

Magnetic Hyperthermia ◽

Antitumor Effects ◽

Functionalized Magnetic Nanoparticles

There is still a need for improving the treatment of breast cancer with doxorubicin (DOX). In this paper, we functionalized magnetic nanoparticles (MNPs) with DOX and studied the DOX-induced antitumor effects in breast cancer cells (BT474) in the presence of magnetic hyperthermia (43 °C, 1 h). We show that i) intratumoral application of DOX-functionalized MNPs (at least at a concentration of 9.6 nmol DOX/100 mm3 tumor volume) combined with magnetic hyperthermia favors tumor regression in vivo, and there is evidence for an increased effect compared to magnetic hyperthermia alone or to the intratumoral application of free DOX and ii) the presence of the pseudopeptide NucAnt (N6L) on the MNP surface might well be beneficial in its function as carrier for MNP internalization into breast cancer cells in vitro, which could further augment the possibility of the induction of intracellular heating spots and cell death in the future.

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10P In vitro and in vivo cytolethal and antitumor effects of a novel fusion protein targeting IL-24 toward breast cancer cells

Annals of Oncology ◽

10.1016/j.annonc.2020.01.058 ◽

2020 ◽

Vol 31 ◽

pp. S2

Author(s):

A. Jahanian-Najafabadi ◽

R. Ghavimi ◽

V. Akbari

Keyword(s):

Breast Cancer ◽

Fusion Protein ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Protein Targeting ◽

Antitumor Effects

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Effect of Resveratrol on Growth of 4T1 Breast Cancer Cells in Vitro and in Vivo

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.2002.6554 ◽

2002 ◽

Vol 291 (4) ◽

pp. 1001-1005 ◽

Cited By ~ 67

Author(s):

Kathleen Bove ◽

David W. Lincoln ◽

Min-Fu Tsan

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

4T1 Breast Cancer

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Indirubin suppresses 4T1 murine breast cancer in vitro and in vivo by induction of ferroptosis and up-regulation of Ptgs2

10.21203/rs.3.rs-390546/v1 ◽

2021 ◽

Author(s):

Xiuping Kuang ◽

Yingnan Jiang ◽

Jiwei Huang ◽

Yongzhi Guo ◽

weixi Li

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Underlying Mechanism ◽

Mechanism Study ◽

Commercial Kits ◽

4T1 Breast Cancer ◽

Gsk 3Β

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.

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