scholarly journals Chemopreventive Potential of DSC Anthocyanins and Total Phenolics Extracted from Dark Sweet Cherry (DSC) Through Modulation of MDA-MB-453 Breast Tumor Proteomic Profile

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 305-305
Author(s):  
Shirley Arbizu ◽  
Giuliana Noratto ◽  
Marjorie Layosa ◽  
Nara N Lage ◽  
Liezl Atienza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Nude Mice ◽  
Breast Cancer Cells ◽  
Sweet Cherry ◽  
Total Phenolics ◽  
Volume Growth ◽  
Cancer Prognosis ◽  
Ki 67 ◽  
Athymic Nude Mice

Abstract Objectives To investigate in vivo the chemopreventive activity of dark sweet cherry (DSC) extracted total phenolics (WE) or fractions enriched in anthocyanins (ACN) or proanthocyanidins (PCN) in athymic nude mice xenografted with MDA-MB-453 breast cancer cells. Methods MDA-MB-453 breast cancer cells (1 × 106 cells) were xenografted into athymic nude mice. Mice were gavaged with WE, ACN, or PCN extracts (150 mg/kg body weight/day) for 36 days followed by animal termination. Main organs and tumors were dissected for protein analyses following standard molecular biology techniques and high-resolution nano-HPLC tandem mass spectrometry. Results Tumor volume growth was suppressed at similar levels by WE, ACN, and PCN compared to controls (C) without signs of toxicity in main organs. Tumor protein analysis revealed ERK1/2 phosphorylation induced by WE, ACN, and PCN at similar levels, which may be linked to apoptosis induction by stress regulated ERK1/2 activation. Immunohistochemistry analysis showed decreased tumor cell proliferation and Ki-67 H-scores with potency WE ≥ ACN ≥ PCN. Differential quantitative proteomic analysis of tumor tissues from ACN and C groups revealed the identity of 71 proteins associated with poor breast cancer prognosis that were expressed only in C group (66 proteins), or upregulated in C group (5 proteins) compared to ACN group (p < 0.05). Conclusions These findings revealed the potential of DSC phenolics for breast cancer invasion and metastasis chemoprevention. Funding Sources This work was supported by the Northwest Cherry Growers, Washington State Fruit Commission.

scholarly journals Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

2021 ◽  
Vol 14 (3) ◽  
pp. 254
Author(s):  
Afnan H. El-Gowily ◽  
Samah A. Loutfy ◽  
Ehab M. M. Ali ◽  
Tarek M. Mohamed ◽  
Mohammed A. Mansour
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mtor Pathway ◽  
Tumor Growth Inhibition ◽  
Autophagic Flux ◽  
Ki 67 ◽  
Mcf 7

Cancer is a complex devastating disease with enormous treatment challenges, including chemo- and radiotherapeutic resistance. Combination therapy demonstrated a promising strategy to target hard-to-treat cancers and sensitize cancer cells to conventional anti-cancer drugs such as doxorubicin. This study aimed to establish molecular profiling and therapeutic efficacy assessment of chloroquine and/or tioconazole (TIC) combination with doxorubicin (DOX) as anew combination model in MCF-7 breast cancer. The drugs are tested against apoptotic/autophagic pathways and related redox status. Molecular docking revealed that chloroquine (CQ) and TIC could be potential PI3K and ATG4B pathway inhibitors. Combination therapy significantly inhibited cancer cell viability, PI3K/AkT/mTOR pathway, and tumor-supporting autophagic flux, however, induced apoptotic pathways and altered nuclear genotoxic feature. Our data revealed that the combination cocktail therapy markedly inhibited tumor proliferation marker (KI-67) and cell growth, along with the accumulation of autophagosomes and elevation of LC3-II and p62 levels indicated autophagic flux blockage and increased apoptosis. Additionally, CQ and/or TIC combination therapy with DOX exerts its activity on the redox balance of cancer cells mediated ROS-dependent apoptosis induction achieved by GPX3 suppression. Besides, Autophagy inhibition causes moderately upregulation in ATGs 5,7 redundant proteins strengthened combinations induced apoptosis, whereas inhibition of PI3K/AKT/mTOR pathway with Beclin-1 upregulation leading to cytodestructive autophagy with overcome drug resistance effectively in curing cancer. Notably, the tumor growth inhibition and various antioxidant effects were observed in vivo. These results suggest CQ and/or TIC combination with DOX could act as effective cocktail therapy targeting autophagy and PI3K/AKT/mTOR pathways in MCF-7 breast cancer cells and hence, sensitizes cancer cells to doxorubicin treatment and combat its toxicity.

scholarly journals Effect of combined therapy with the antiestrogen agent toremifene and local hyperthermia on breast cancer cells implanted in nude mice

Surgery Today ◽  
2008 ◽  
Vol 38 (10) ◽  
pp. 911-920 ◽  
Author(s):  
Yoshiaki Kanaya ◽  
Hiroyoshi Doihara ◽  
Kouji Shiroma ◽  
Yutaka Ogasawara ◽  
Hiroshi Date
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Nude Mice ◽  
Breast Cancer Cells ◽  
Combined Therapy ◽  
Local Hyperthermia

scholarly journals Asiatic Acid Interferes with Invasion and Proliferation of Breast Cancer Cells by Inhibiting WAVE3 Activation through PI3K/AKT Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Xiao-jun Gou ◽  
Huan-huan Bai ◽  
Li-wei Liu ◽  
Hong-yu Chen ◽  
Qi Shi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Nude Mice ◽  
Breast Cancer Cells ◽  
Akt Signaling ◽  
Asiatic Acid ◽  
Akt Signaling Pathway ◽  
Xenografted Tumor

Objective. To explore the ability of asiatic acid to interfere with the invasion and proliferation of breast cancer cells by inhibiting WAVE3 expression and activation through the PI3K/AKT signaling pathway. Methods. The MDA-MB-231 cells with strong invasiveness were screened by transwell assay, and plasmids with high expression of WAVE3 were constructed for transfection. The transfection effect and protein expression level of plasmids were verified by PCR and WB. The effects of asiatic acid on cell proliferation and invasion were investigated by flow cytometry. The xenografted tumor models in nude mice were established to study the antitumor activity of asiatic acid. Results. Asiatic acid significantly inhibited the activity of MDA-MB-231 cells, and the expression level of WAVE3 increased significantly in the tissue of ductal carcinoma in situ and was lower than that in the metastasis group. After plasmid transfection, the mRNA and protein expression of WAVE3 increased significantly in the cells. Asiatic acid at different concentrations had an impact on cell apoptosis and invasion and could significantly inhibit the expression of WAVE3, P53, p-PI3K, p-AKT, and other proteins. The T/C(%) of asiatic acid (50 mg/kg) for MDA-MB-231(F10) xenografted tumor in nude mice was 46.33%, with a tumor inhibition rate of 59.55%. Asiatic acid could significantly inhibit the growth of MDA-MB-231 (F10) xenografted tumors in nude mice (p<0.05). Conclusions. Asiatic acid interferes with the ability of breast cancer cells to invade and proliferate by inhibiting WAVE3 expression and activation and the mechanism of action may be related to the PI3K/AKT signaling pathway.

scholarly journals APR-246 alone and in combination with a phosphatidylserine-targeting antibody inhibits lung metastasis of human triple-negative breast cancer cells in nude mice

2019 ◽  
Vol Volume 11 ◽  
pp. 249-259
Author(s):  
Yayun Liang ◽  
Cynthia Besch-Williford ◽  
Matthew T Cook ◽  
Anthony Belenchia ◽  
Rolf A Brekken ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Lung Metastasis ◽  
Triple Negative Breast Cancer ◽  
Nude Mice ◽  
Breast Cancer Cells ◽  
Triple Negative
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