CARBON NANOHORN AS NANOCONTAINER FOR CISPLATIN: INSIGHTS ON THE INTERACTION WITH PLASMA MEMBRANES OF NORMAL AND BREAST CANCER CELLS

Author(s):  
Eduardo Ribeiro Almeida ◽  
Helio F. Dos Santos ◽  
Priscila V. S. Z. Capriles

Cisplatin (cddp)-based chemotherapy is one of the most effective therapeutic alternatives for breast cancer treatment, the most common form of cancer, despite the severe side effects related to the high...

2018 ◽  
Vol 47 (6) ◽  
pp. 2199-2215 ◽  
Author(s):  
Jian Hao ◽  
Ziqi Jin ◽  
Hongxu Zhu ◽  
Xiaohui Liu ◽  
Yu Mao ◽  
...  

Background/Aims: The Xi-Huang (XH) formula has been used for breast cancer treatment in traditional Chinese medicine (TCM) since 1740. In this study, we show that, XH extract could suppress the growth of breast cancer cells in vitro and in vivo, and that it preferentially inhibits cell growth of estrogen receptor positive (ER+) breast cancer cells. Presently, little is known about the potential mechanism of XH and our studies aim to elucidate its mechanism in breast cancer treatment. Methods: Network-based systems biology and molecular docking analyses were performed to predict explicit targets of XH and active ingredients in XH. The effects of XH on cell viability, cell cycle, apoptosis in different breast cancer cell lines were analyzed in vitro. A model of transplanted tumors on nude mice was used to study the anticancer effect in vivo. Various techniques, including western blotting, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, co-immunoprecipitation and immunohistochemical were utilized to assess the expression of targets of XH in vitro and in vivo. RNA sequencing (RNA-seq) was performed to study the gene targets of XH. Furthermore, we analyzed of protein-ligand binding reactions by isothermal titration calorimetry (ITC). Results: Using network-based systems biology and molecular docking analyses, we predicted that the major targets of XH were ERα and HSP90. Moreover, we found that, XH mediated its anti-cancer effects by promoting the disassociation of ERα and HSP90, resulting in the degradation of ERα and blockade of transport of ERα to the nucleus. XH also caused the dissociation of ERα and other oncoproteins via binding to HSP90. Some of the active ingredients in XH share a common cyclopentane hydrogen skeleton and were predicted to target ERα based on the structural similarity. Conclusions: XH, which has been used since 1740, has antiestrogenic effects in breast cancer via the targeting of ERα.


2020 ◽  
Author(s):  
yongxia chen ◽  
yunlu jia ◽  
misha mao ◽  
Yifeng Gu ◽  
Chenpu Xu ◽  
...  

Abstract Background Adriamycin (ADM) is currently one of the most effective chemotherapeutic agents in breast cancer treatment. However, growing resistance to ADM can lead to treatment failure and poor outcome. The underlying molecular mechanisms in ADM resistance in breast cancer remains unclear. PLAC8 is reported as a novel highly-conserved protein and functions as an oncogene or tumor suppressor in various tumors. Methods Here, we analyzed the expression profile of PLAC8 in breast cancer tissues and breast cancer cell lines, and explored the correlation of PLAC8 expression levels with patients’ outcomes and ADM response. One ADM resistant MCF-7 breast cancer cell (MCF-7/ADM) and its parental cell was used as in vitro models to identify the underlying mechanism of PLAC8 and ADM resistance. Breast cancer cells were transfected with PLAC8 knockdown and overexpression vectors, and MTT and colony formation assays were performed to test the cell response to ADM. Then, we tested the effect of PLAC8 on autophagy pathway by flow cytometry and immunofluorescence analysis, and the change of main autophagy-correlated factors expressions: LC3 and p62. Next, combining treatment of autophagy inhibitor/inducer and PLAC8 downregulation/upregulation revealed the participation of PLAC8 in autophagy pathway to synergistically regulate ADM resistance in breast cancer. Results Here, higher PLAC8 expression was correlated with poorer outcome and aggressive phenotype in breast cancer, and breast cancer patients with higher PLAC8 expression showed potential ADM resistance. PLAC8 expression level was also significantly elevated in ADM resistant MCF-7 breast cancer cells (MCF-7/ADM), compared to parental MCF-7 cells. In vitro experiments further confirmed that PLAC8 inhibition by siRNA or enforced overexpression by infecting pcDNA3.1(C)-PLAC8 plasmid correspondingly decreased or increased the ADM resistance. Subsequently, we demonstrated that ectopic PLAC8 expression in MCF-7/ADM cell blocked the accumulation of the autophagy-associated protein LC3II, and resulted in cellular accumulation of p62. Rapamycin-triggered autophagy significantly increased cell response to ADM, while the autophagy inhibitor 3-MA enhanced ADM resistance. Actually, 3-MA and PLAC8 could synergistically enhance ADM resistance via blocking the autophagy process. Additionally, the downregulation of p62 by siRNA attenuated the activation of autophagy and PLAC8 expression in breast cancer cells. Conclusion Our findings suggest that PLAC8, through participation of p62, inhibits autophagy and consequently results in ADM resistance in breast cancer. PLAC8/p62/autophagy pathway may act as novel therapeutic targets in breast cancer treatment and has potential clinical application in overcoming ADM resistance.


2021 ◽  
Vol 11 ◽  
Author(s):  
Shengqi Wang ◽  
Xu Chang ◽  
Juping Zhang ◽  
Jing Li ◽  
Neng Wang ◽  
...  

Breast cancer remains the most common malignancy and the leading causality of cancer-associated mortality among women worldwide. With proven efficacy, Oldenlandia diffusa has been extensively applied in breast cancer treatment in Traditional Chinese Medicine (TCM) for thousands of years. However, the bioactive compounds of Oldenlandia diffusa accounting for its anti-breast cancer activity and the underlying biological mechanisms remain to be uncovered. Herein, bioactivity-guided fractionation suggested ursolic acid as the strongest anti-breast cancer compound in Oldenlandia diffusa. Ursolic acid treatment dramatically suppressed the proliferation and promoted mitochondrial-mediated apoptosis in breast cancer cells while brought little cytotoxicities in nonmalignant mammary epithelial cells in vitro. Meanwhile, ursolic acid dramatically impaired both the glycolytic metabolism and mitochondrial respiration function of breast cancer cells. Further investigations demonstrated that ursolic acid may impair the glycolytic metabolism of breast cancer cells by activating Caveolin-1 (Cav-1) signaling, as Cav-1 knockdown could partially abrogate the suppressive effect of ursolic acid on that. Mechanistically, ursolic acid could activate SP1-mediated CAV1 transcription by promoting SP1 expression as well as its binding with CAV1 promoter region. More meaningfully, ursolic acid administration could dramatically suppress the growth and metastasis of breast cancer in both the zebrafish and mouse xenotransplantation models of breast cancer in vivo without any detectable hepatotoxicity, nephrotoxicity or hematotoxicity. This study not only provides preclinical evidence supporting the application of ursolic acid as a promising candidate drug for breast cancer treatment but also sheds novel light on Cav-1 as a druggable target for glycolytic modulation of breast cancer.


Author(s):  
Camila Salata ◽  
Carlos E. deAlmeida ◽  
Samara C. Ferreira-Machado ◽  
Regina C. Barroso ◽  
Liebert P Nogueira ◽  
...  

2012 ◽  
Vol 27 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Sarah Schmalenberger ◽  
Charles E Gessert ◽  
Jean E Giebenhain ◽  
Lisa D Starr

The Life and Livelihood Study was designed to describe and understand the experience of women musicians treated for breast cancer. This report focuses on Phase I of the study, a web-based survey that examined subjects’ physical symptoms and side effects following breast cancer treatment. Subjects were recruited nationally, using advertisements in musicians’ publications and presentations at national meetings. Subjects were asked about specific side effects or symptoms they had experienced, their severity and duration, and the effects of symptoms on their capacity to make music. Subjects were also asked what aspect of their breast cancer treatment they associated with each symptom and were invited to provide comments. A total of 321 individuals logged on: 100 met all inclusion criteria. Of these, 90 completed the entire survey. Commonly reported symptoms included fatigue (70%), problems with cognition (53%), limitations in upper body movement (51%), and pain (45%). Many reported that their symptoms were of moderate or greater intensity, and that they persisted for >12 months or were ongoing. The survey documented that many subjects experienced diminished capacity to function as musicians, especially due to pain, limitations in upper body and extremity movement, numbness in the chest and/or arms, contracture/fibrosis, and shortness of breath. These findings are consistent with emerging studies that describe long-term effects of breast cancer treatments. In planning for breast cancer treatment, rehabilitation and survivorship, consideration should be given to how treatment is likely to affect fitness for ongoing professional work.


Processes ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1110
Author(s):  
Minh Thanh Vu ◽  
Dinh Tien Dung Nguyen ◽  
Ngoc Hoi Nguyen ◽  
Van Thu Le ◽  
The Nam Dao ◽  
...  

Paclitaxel (PTX) and anastrozole (ANA) have been frequently applied in breast cancer treatment. PTX is well-known for its anti-proliferative effect meanwhile ANA has just been discovered to act as an estrogen receptor α (ERα) ligand. The combination therapy of PTX and ANA is expected to improve treating efficiency, as ANA would act as a ligand binding with the ERα gene expressed in breast cancer cells and thereafter PTX would inhibit the division and cause death to those cancer cells. In this study, liposome-based nanocarriers (LP) were developed for co-encapsulation of PTX and ANA to improve the efficacy of the combined drugs in an Estrogen receptor-responsive breast cancer study. PTX-ANA co-loaded LP was prepared using thin lipid film hydration method and was characterized for morphology, size, zeta potential, drug encapsulation and in vitro drug release. In addition, cell proliferation (WST assay) and IN Cell Analyzer were used for in vitro cytotoxicity studies on a human breast cancer cell line (MCF-7). Results showed that the prepared LP and PTX-ANA-LP had spherical vesicles, with a mean particle size of 170.1 ± 13.5 nm and 189.0 ± 22.1 nm, respectively. Controlled and sustained releases were achieved at 72 h for both of the loaded drugs. The in vitro cytotoxicity study found that the combined drugs showed higher toxicity than each single drug separately. These results suggested a new approach to breast cancer treatment, consisting of the combination therapy of PTX and ANA in liposomes based on ER response.


2019 ◽  
Vol 9 (8) ◽  
pp. 882-894
Author(s):  
Jahnavi Rama Madhuri Kamaraju ◽  
Raghavendra Rao Kanchi ◽  
Rajesh Kumar Borra ◽  
Padma Suvarna Reniguntla ◽  
Satyanarayana Rentala

Nanophosphor compounds with both diagnostic and therapeutic functions are potential for cancer diagnosis and treatment. Lanthanide complexes play a crucial role in cancer diagnosis and therapy. Gadolinium-complexes are commonly used as magnetic resonance imaging (MRI) contrast agents for cancer imaging. The role of a lanthanide, Ytterbium (Yb) in cancer treatment is not unknown. The present work focuses on finding the role of Yb when doped into Gadolinium complexes in cancer treatment. Our results demonstrate that Yb doped Gadolinium molybdate coated with biocompatible silica, effectively inhibited the viability of breast cancer cells after 24 and 48 h of treatment in in vitro, and in contrast the nanophosphor compounds did not affect the viability of healthy cells. Yb doped Gadolinium molybdate also up-regulated apoptotic genes in breast cancer cells. Hence we propose that Yb doped Gadolinium molybdate is a promising theranostic compound. To the best of our knowledge, this is the first report showing anti-cancer nature of Ytterbium-doped into Gadolinium nanophosphors.


2010 ◽  
Vol 22 (2) ◽  
pp. 81-97 ◽  
Author(s):  
Stephanie Dos Santos ◽  
Nancy Hill ◽  
Ashley Morgan ◽  
Jenna Smith ◽  
Carolyn Thai ◽  
...  

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