Polymalic Acid–Based Nanobiopolymer Provides Efficient Systemic Breast Cancer Treatment by Inhibiting both HER2/neu Receptor Synthesis and Activity

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumor Growth Inhibition ◽  
Human Breast ◽  
Akt Phosphorylation

Biodegradable nanopolymers are believed to offer great potential in cancer therapy. Here, we report thecharacterization of a novel, targeted, nanobiopolymeric conjugate based on biodegradable, nontoxic, andnonimmunogenic PMLA [poly(b-L-malic acid)]. The PMLA nanoplatform was synthesized for repetitive systemictreatments of HER2/neu-positive human breast tumors in a xenogeneic mouse model. Various moieties werecovalently attached to PMLA, including a combination of morpholino antisense oligonucleotides (AON) directedagainst HER2/neu mRNA, to block new HER2/neu receptor synthesis; anti-HER2/neu antibody trastuzumab(Herceptin), to target breast cancer cells and inhibit receptor activity simultaneously; and transferrin receptorantibody, to target the tumor vasculature and mediate delivery of the nanobiopolymer through the hostendothelial system. The results of the study showed that the lead drug tested significantly inhibited the growth ofHER2/neu-positive breast cancer cells in vitro and in vivo by enhanced apoptosis and inhibition of HER2/neureceptor signaling with suppression of Akt phosphorylation. In vivo imaging analysis and confocal microscopydemonstrated selective accumulation of the nanodrug in tumor cells via an active delivery mechanism. Systemictreatment of human breast tumor-bearing nude mice resulted in more than 90% inhibition of tumor growth andtumor regression, as compared with partial (50%) tumor growth inhibition in mice treated with trastuzumab orAON, either free or attached to PMLA. Our findings offer a preclinical proof of concept for use of the PMLAnanoplatform for combination cancer therapy.

Clomiphene Analogs with Activity In Vitro and In Vivo against Human Breast Cancer Cells

1998 ◽  
Vol 55 (6) ◽  
pp. 841-851 ◽  
Author(s):  
R.Jeffrey Baumann ◽  
Tammy L. Bush ◽  
Doreen E. Cross-Doersen ◽  
Elizabeth A. Cashman ◽  
Paul S. Wright ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast

scholarly journals Mead acid inhibits the growth of KPL-1 human breast cancer cells in vitro and in vivo

2014 ◽  
Vol 32 (4) ◽  
pp. 1385-1394 ◽  
Author(s):  
YUICHI KINOSHITA ◽  
KATSUHIKO YOSHIZAWA ◽  
KEI HAMAZAKI ◽  
YUKO EMOTO ◽  
TAKASHI YURI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mead Acid

scholarly journals α-Tocopherol succinate enhances pterostilbene anti-tumor activity in human breast cancer cells in vivo and in vitro

Oncotarget ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 4593-4606 ◽  
Author(s):  
Ka-Wai Tam ◽  
Chi-Tang Ho ◽  
Shih-Hsin Tu ◽  
Wen-Jui Lee ◽  
Ching-Shui Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Anti Tumor Activity

scholarly journals tRNA Queuosine Modification Enzyme Modulates the Growth and Microbiome Recruitment to Breast Tumors

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 628
Author(s):  
Jilei Zhang ◽  
Rong Lu ◽  
Yongguo Zhang ◽  
Żaneta Matuszek ◽  
Wen Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
And Migration

Background: Transfer RNA (tRNA) queuosine (Q)-modifications occur specifically in 4 cellular tRNAs at the wobble anticodon position. tRNA Q-modification in human cells depends on the gut microbiome because the microbiome product queuine is required for its installation by the enzyme Q tRNA ribosyltransferase catalytic subunit 1 (QTRT1) encoded in the human genome. Queuine is a micronutrient from diet and microbiome. Although tRNA Q-modification has been studied for a long time regarding its properties in decoding and tRNA fragment generation, how QTRT1 affects tumorigenesis and the microbiome is still poorly understood. Results: We generated single clones of QTRT1-knockout breast cancer MCF7 cells using Double Nickase Plasmid. We also established a QTRT1-knockdown breast MDA-MB-231 cell line. The impacts of QTRT1 deletion or reduction on cell proliferation and migration in vitro were evaluated using cell culture, while the regulations on tumor growth in vivo were evaluated using a xenograft BALB/c nude mouse model. We found that QTRT1 deficiency in human breast cancer cells could change the functions of regulation genes, which are critical in cell proliferation, tight junction formation, and migration in human breast cancer cells in vitro and a breast tumor mouse model in vivo. We identified that several core bacteria, such as Lachnospiraceae, Lactobacillus, and Alistipes, were markedly changed in mice post injection with breast cancer cells. The relative abundance of bacteria in tumors induced from wildtype cells was significantly higher than those of QTRT1 deficiency cells. Conclusions: Our results demonstrate that the QTRT1 gene and tRNA Q-modification altered cell proliferation, junctions, and microbiome in tumors and the intestine, thus playing a critical role in breast cancer development.

Estrogen receptor β represses breast tumor growth and angiogenesis in vivo

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10101-10101
Author(s):  
J. Hartman ◽  
K. Lindberg ◽  
J. Inzunza ◽  
J. Wan ◽  
A. Ström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth ◽  
Angiogenic Effect

10101 Background: Estrogens are well known stimulators of breast cancer cell growth in vitro as well as in vivo. Two different estrogen receptors exist, namely estrogen receptor (ER) α and β. ERα mediates the proliferative effect of estrogen in breast cancer cells and we have earlier shown that ERβ inhibits cell-cycle progression in vitro. Estrogens are well known stimulators of in vivo breast cancer cell growth as well as angiogenesis, and the effect is mediated through ERα. The function of ERβ in this context is not well understood. Methods: We have used ERα-positive T47D breast cancer cells stably transfected with a Tet/Off regulated ERβ expression vector system. The ERβ-inducible tumor cells are studied in vitro as well as in vivo. Results: By transplanting ERβ-inducible breast cancer cells into SCID-mice, we show that ERβ inhibits tumor growth and reduces the volume of established tumors. Furthermore, we show by immunohistochemistry, that the number of blood microvessels in the tumor periphery is decreased by ERβ expression, counteracting the well-known pro-angiogenic effect of ERα. By Western blot analysis on tumor extracts, we show that the concentration of the important pro-angiogenic growth factors VEGF and bFGF, normally expressed by breast tumor cells, is decreased in the ERβ-expressing tumors compared to the normal tumors. To exclude that the observed anti-angiogenic effect is just a result of reduced tumor growth, we incubated Tet/Off regulated ERβ expressing cells in vitro, during non-hypoxic conditions. We found that the expression of ERβ leads to decreased expression of VEGF and PDGFβ at the mRNA and protein-levels. In transient transfection assays, we found estrogen-ERα mediated up regulation of VEGF, PDGFβ and bFGF-promoter activities in T47D cells, and these activities were all suppressed following co-transfection with an ERβ-expression vector. Conclusions: We conclude that ERβ inhibits growth factor expression at transcriptional level in breast cancer cells; taken together, our data indicates that ERβ inhibits growth and angiogenesis of tumors formed by T47D breast cancer cells. This makes ERβ an interesting therapeutic target in breast cancer and perhaps treatment with the newly designed ERβ-selective ligands might work as a new anti-proliferative and anti-angiogenic therapy. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document