scholarly journals DNA-based nanoscaffolds as vehicles for 5-fluoro-2′-deoxyuridine oligomers in colorectal cancer therapy

Nanoscale ◽  
2018 ◽  
Vol 10 (15) ◽  
pp. 7238-7249 ◽  
Author(s):  
A. F. Jorge ◽  
A. Aviñó ◽  
A. A. C. C. Pais ◽  
R. Eritja ◽  
C. Fàbrega
Keyword(s):  
Colorectal Cancer ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Anticancer Drug ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Dna Tetrahedron ◽  
Drug Nanocarriers

A novel application for DNA nanostructures as anticancer drug nanocarriers is proposed. DNA tetrahedron and rectangle DNA origami were exploited to deliver 5-fluoro-2′-deoxyuridine oligomers, aided by cholesterol moieties, into 5-fluorouracil-resistant cancer cells.

Nature of the charged head group dictates the anticancer potential of lithocholic acid-tamoxifen conjugates for breast cancer therapy

MedChemComm ◽  
2015 ◽  
Vol 6 (5) ◽  
pp. 778-787 ◽  
Author(s):  
Kavita Yadav ◽  
Priyanshu Bhargava ◽  
Sandhya Bansal ◽  
Manish Singh ◽  
Siddhi Gupta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Anticancer Drug ◽  
Breast Cancer Cells ◽  
Lithocholic Acid ◽  
Head Group ◽  
Breast Cancer Therapy

Anticancer drug Tamoxifen is modified to charged lithocholic acid derived amphiphile for enhanced cytotoxicity against breast cancer cells.

scholarly journals Protecting microRNAs from RNase degradation with steric DNA nanostructures

2017 ◽  
Vol 8 (2) ◽  
pp. 1062-1067 ◽  
Author(s):  
H. Qian ◽  
C. Y. Tay ◽  
M. I. Setyawati ◽  
S. L. Chia ◽  
D. S. Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Dna Nanostructures ◽  
Human Colorectal Cancer ◽  
Dna Nanostructure ◽  
Colorectal Cancer Cells ◽  
Therapeutic Platform ◽  
Human Colorectal Cancer Cells

A DNA nanostructure bearing a “Shuriken” shape is designed to deliver, protect and activate microRNA-145 functionality in human colorectal cancer cells. This novel DNA nanostructure enabled therapeutic platform greatly suppresses cancer cell proliferation and tumor growth.

scholarly journals Site-specific anchoring aptamer C2NP on DNA origami nanostructures for cancer treatment

RSC Advances ◽  
2018 ◽  
Vol 8 (46) ◽  
pp. 26300-26308 ◽  
Author(s):  
Pengchao Sun ◽  
Nan Zhang ◽  
Yafang Tang ◽  
Yanan Yang ◽  
Jie Zhou ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Treatment ◽  
Anticancer Activity ◽  
Biological Effect ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Site Specific

Aptamer anchored DNA nanostructures not only can enhance the anticancer activity of DOX, but also exhibit synergic biological effect with chemotherapy on cancer therapy.

scholarly journals Mithramycin A Inhibits Colorectal Cancer Growth by Targeting Cancer Stem Cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Waise Quarni ◽  
Rinku Dutta ◽  
Ryan Green ◽  
Sandhyabanu Katiri ◽  
Bhaumik Patel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Ex Vivo ◽  
Parp Cleavage ◽  
Cancer Growth ◽  
Mithramycin A ◽  
Total Cancer

Abstract The pivotal role of cancer initiating stem cells (CSCs) in tumor initiation, growth, metastasis and drug resistance has led to the postulation of a ‘total cancer therapy’ paradigm, which involves targeting both cancer cells and CSCs for effective therapy. However, the progress in identifying drugs for total cancer therapy has been limited. Herein, we show for the first time that mithramycin A (Mit-A) can successfully inhibit CSC proliferation, in addition to inhibiting bulk cancer cells in a model of colorectal cancer (CRC), the second leading cause of death among men and women in the United States. To this end, a polymeric nanofiber scaffold culture system was established to develop 3D tumor organoids (tumoroids) from CRC cell lines such as HT29, HCT116, KM12, CT26 and MC38 as well as ex vivo mouse tumors. These tumoroids possessed increased expression of CSC markers and transcription factors, expanded the number of CSCs in culture and increased CSC functional properties measured by aldehyde dehydrogenase activity. Screening of an NCI library of FDA approved drugs led to the identification of Mit-A as a potential total cancer therapy drug. In both sphere and tumoroid culture, Mit-A inhibits cancer growth by reducing the expression of cancer stemness markers. In addition, Mit-A inhibits the expression of SP1, a previously known target in CRCs. Moreover, Mit-A significantly reduces growth of tumoroids in ex vivo cultures and CRC tumor growth in vivo. Finally, a dose-dependent treatment on CRC cells indicate that Mit-A significantly induces the cell death and PARP-cleavage of both CSC and non-CSC cells. Taken together the results of these in vitro, ex vivo and in vivo studies lead to the inference that Mit-A is a promising drug candidate for total cancer therapy of CRCs.

Bifunctional magnetopolymersomes of iron oxide nanoparticles and carboxymethylcellulose conjugated with doxorubicin for hyperthermo-chemotherapy of brain cancer cells

2019 ◽  
Vol 7 (5) ◽  
pp. 2102-2122 ◽  
Author(s):  
Sandhra M. Carvalho ◽  
Alice G. Leonel ◽  
Alexandra A. P. Mansur ◽  
Isadora C. Carvalho ◽  
Klaus Krambrock ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Iron Oxide Nanoparticles ◽  
Brain Cancer ◽  
Oxide Nanoparticles ◽  
Drug Nanocarriers

Magnetopolymersomes for potential multimodal brain cancer therapy – “nanoheaters meet drug nanocarriers”.

scholarly journals Biocompatible pH-responsive nanoparticles with a core-anchored multilayer shell of triblock copolymers for enhanced cancer therapy

2017 ◽  
Vol 5 (23) ◽  
pp. 4421-4425 ◽  
Author(s):  
Elizabeth Ellis ◽  
Kangyi Zhang ◽  
Qianyu Lin ◽  
Enyi Ye ◽  
Alessandro Poma ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Self Assembly ◽  
Triblock Copolymers ◽  
Drug Efficacy ◽  
Multilayer Shell ◽  
Ph Responsive ◽  
Drug Nanocarriers ◽  
Excellent Stability

pH-Responsive drug nanocarriers were made via facile self-assembly, showing excellent stability in bio-media (50% PBS/FBS) and enhanced drug efficacy towards cancer cells.

scholarly journals Efficacy of the MEK Inhibitor Cobimetinib and its Potential Application to Colorectal Cancer Cells

2018 ◽  
Vol 47 (2) ◽  
pp. 680-693 ◽  
Author(s):  
Shu Gong ◽  
Dongsheng Xu ◽  
Jialin Zhu ◽  
Fangdong Zou ◽  
Rui Peng
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Dna Replication ◽  
Cancer Therapy ◽  
Cell Viability ◽  
Cancer Cells ◽  
Mek Inhibitor ◽  
Colorectal Cancer Cells ◽  
Cancer Tissues ◽  
Hct116 Cells

Background/Aims: Mutations in the Ras/Raf/MEK/ERK pathway are detected in 50% of colorectal cancer cases and play a crucial role in cancer development and progression. Cobimetinib is a MEK inhibitor approved for the treatment of advanced melanoma and inhibits the cell viability of other types of cancer cells. Methods: HCT116 colorectal cancer cells were treated with cobimetinib, and MTT assay, colony formation assay, and flow cytometry were used to evaluate cell viability, cell cycle, and apoptosis, respectively. The expression of genes associated with the cell cycle and apoptosis were evaluated by quantitative real-time PCR and western blotting. To explore use of cobimetinib in colorectal cancer treatment and further understand its mechanisms, RNA-seq technology was used to identify differentially expressed genes (DEGs) between cobimetinib-treated and untreated HCT116 cells. Furthermore, we compared these DEGs with Gene Expression Omnibus data from colorectal cancer tissues and normal colonic epithelial tissues. Results: We found that cobimetinib not only inhibited cell proliferation but also induced G1 phase arrest and apoptosis in HCT116 colorectal cancer cells, suggesting that cobimetinib may useful in colorectal cancer therapy. After cobimetinib treatment, 3,495 DEGs were obtained, including 2,089 upregulated genes and 1,406 downregulated genes, and most of these DEGs were enriched in the cell cycle, DNA replication, and DNA damage repair pathways. Our results revealed that some genes with high expression in colorectal cancer tissues were downregulated by cobimetinib in HCT116 cells, including CCND1, E2F1, CDC25C, CCNE2, MYC, and PCNA. These genes have vital roles in DNA replication and the cell cycle. Furthermore, genes with low expression in colorectal cancer tissues were upregulated by cobimetinib, including PRKCA, PI3K, RTK, and PKC. Based on our results, the PKC and PI3K pathways were activated after cobimetinib treatment, and inhibition of these two pathways can increase the cytotoxicity of cobimetinib in HCT116 cells. Notably, cobimetinib appeared to enhance the efficacy of 5-fluorouracil (5-FU) by decreasing TYMS expression, high expression of which is responsible for 5-FU resistance in colorectal cancer. Conclusions: Our results suggest the potential use of cobimetinib in colorectal cancer therapy.

scholarly journals Discovery of a novel ferroptosis inducer-talaroconvolutin A—killing colorectal cancer cells in vitro and in vivo

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Yong Xia ◽  
Shuzhi Liu ◽  
Changlin Li ◽  
Zhiying Ai ◽  
Wenzhi Shen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Drug Candidate ◽  
In Vivo Experiments ◽  
Colorectal Cancer Cells ◽  
Liver And Kidney ◽  
Cancer Suppression

AbstractFerropotsis is among the most important mechanisms of cancer suppression, which could be harnessed for cancer therapy. However, no natural small-molecule compounds with cancer inhibitory activity have been identified to date. In the present study, we reported the discovery of a novel ferroptosis inducer, talaroconvolutin A (TalaA), and the underlying molecular mechanism. We discovered that TalaA killed colorectal cancer cells in dose-dependent and time-dependent manners. Interestingly, TalaA did not induce apoptosis, but strongly triggered ferroptosis. Notably, TalaA was significantly more effective than erastin (a well-known ferroptosis inducer) in suppressing colorectal cancer cells via ferroptosis. We revealed a dual mechanism of TalaA’ action against cancer. On the one hand, TalaA considerably increased reactive oxygen species levels to a certain threshold, the exceeding of which induced ferroptosis. On the other hand, this compound downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. Furthermore, in vivo experiments in mice evidenced that TalaA effectively suppressed the growth of xenografted colorectal cancer cells without obvious liver and kidney toxicities. The findings of this study indicated that TalaA could be a new potential powerful drug candidate for colorectal cancer therapy due to its outstanding ability to kill colorectal cancer cells via ferroptosis induction.

A new biosafe reactive oxygen species (ROS)-responsive nanoplatform for drug delivery

RSC Advances ◽  
2016 ◽  
Vol 6 (45) ◽  
pp. 38984-38989 ◽  
Author(s):  
Qing Li ◽  
Yong Wen ◽  
Jie Wen ◽  
Yun-Peng Zhang ◽  
Xiao-Ding Xu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Drug Delivery ◽  
Cancer Therapy ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Anticancer Drug ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Rapid Release ◽  
Oral Cancer Cells

.A new ROS-responsive nanoplatform was deleveloped to load anticancer drug for oral cancer therapy. The ROS in cytoplasm can efficiently destroy the nanoplatform, leading to a rapid release of loaded drug and apoptosis of oral cancer cells.

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