Synthesis and immunological evaluation of the unnatural β-linked mucin-1 Thomsen–Friedenreich conjugate

2021 ◽  
Vol 19 (11) ◽  
pp. 2448-2455
Author(s):  
Xuanjun Wu ◽  
Hunter McFall-Boegeman ◽  
Zahra Rashidijahanabad ◽  
Kunli Liu ◽  
Christian Pett ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Igg Antibodies ◽  
Mucin 1 ◽  
Peptide Backbone ◽  
Glycoprotein P ◽  
Immunological Evaluation ◽  
Muc1 Glycoprotein

A MUC1 glycopeptide bearing an unnatural β-glycosyl bond between the glycan and the peptide backbone was synthesized. The mimic can induce high levels of IgG antibodies cross-recognizing cancer cells expressing the native MUC1 glycoprotein.

scholarly journals pH-Sensitive Poly(β-amino ester)s Nanocarriers Facilitate the Inhibition of Drug Resistance in Breast Cancer Cells

Nanomaterials ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 952 ◽  
Author(s):  
Mengxue Zhou ◽  
Xingcai Zhang ◽  
Jin Xie ◽  
Rongxiang Qi ◽  
Huiru Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Ph Sensitive ◽  
Amino Ester ◽  
Stimuli Responsive ◽  
Glycoprotein P ◽  
Cell Internalization ◽  
Promising Tool ◽  
Intracellular Drug Delivery ◽  
Mcf 7

Multidrug resistance (MDR) remains an unmet challenge in chemotherapy. Stimuli-responsive nanocarriers emerge as a promising tool to overcome MDR. Herein, pH-sensitive poly(β-amino ester)s polymers (PHP)-based micellar nanoparticles were synthesized for enhanced doxorubicin (DOX) delivery in drug resistant breast cancer MCF-7/ADR cells. DOX-loaded PHP micelles showed rapid cell-internalization and lysosomal escape in MCF-7/ADR cells. The cytotoxicity assays showed relatively higher cell inhibition of DOX-loaded PHP micelles than that of free DOX against MCF-7/ADR cells. Further mechanistic studies showed that PHP micelles were able to inhibit P-glycoprotein (P-gp) activity by lowering mitochondrial membrane potentials and ATP levels. These results suggested that the enhanced antitumor effect might be attributed to PHP-mediated lysosomal escape and drug efflux inhibition. Therefore, PHP would be a promising pH-responsive nanocarrier for enhanced intracellular drug delivery and overcoming MDR in cancer cells.

DJ-1 is involved in the multidrug resistance of SGC7901 gastric cancer cells through PTEN/PI3K/Akt/Nrf2 pathway

2020 ◽  
Vol 52 (11) ◽  
pp. 1202-1214
Author(s):  
Lejia Qiu ◽  
Zhaoxia Ma ◽  
Xiaoran Li ◽  
Yizhang Deng ◽  
Guangling Duan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Gastric Cancer Cells ◽  
Glycoprotein P ◽  
Nrf2 Pathway ◽  
P Glycoprotein ◽  
New Findings ◽  
Nrf2 Signaling Pathway ◽  
Common Malignancy

Abstract Gastric cancer is a common malignancy worldwide. The occurrence of multidrug resistance (MDR) is the major obstacle for effective gastric cancer chemotherapy. In this study, the in-depth molecular mechanism of the DJ-1-induced MDR in SGC7901 gastric cancer cells was investigated. The results showed that DJ-1 expression level was higher in MDR variant SGC7901/VCR cells than that in its parental SGC7901 cells. Moreover, DJ-1 overexpression conferred the MDR phenotype to SGC7901 cells, while DJ-1 knockdown in SGC7901/VCR cells induced re-sensitization to adriamycin, vincristine, cisplatin, and 5-fluorouracil. These results suggested that DJ-1 mediated the development of MDR in SGC7901 gastric cancer cells. Importantly, further data revealed that the activation of PI3k/Akt and Nrf2 signaling pathway were required for the DJ-1-induced MDR phenotype in SGC7901 gastric cancer cells. Meanwhile, we found that PI3k/Akt pathway was activated probably through DJ-1 directly binding to and negatively regulating PTEN, consequently resulting in Nrf2 phosphorylation and activation, and thereby inducing Nrf2-dependent P-glycoprotein (P-gp) and Bcl-2 expressions in the DJ-1-mediated MDR of SGC7901 gastric cancer cells. Overall, these results revealed that activating PTEN/PI3K/Akt/Nrf2 pathway and subsequently upregulating P-gp and Bcl-2 expression could be a critical mechanism by which DJ-1 mediates the development of MDR in SGC7901 gastric cancer cells. The new findings may be helpful for understanding the mechanisms of MDR in gastric cancer cells, prompting its further investigation as a molecular target to overcome MDR.

A Boronic Acid Assay for the Detection of Mucin-1 Glycoprotein from Cancer Cells

ChemBioChem ◽  
2017 ◽  
Vol 18 (16) ◽  
pp. 1578-1582 ◽  
Author(s):  
Xiaoyu Zhang ◽  
Shiqiang Zhang ◽  
Seung Joon Baek ◽  
Michael D. Best
Keyword(s):  
Cancer Cells ◽  
Boronic Acid ◽  
Mucin 1

scholarly journals A Novel Approach of Targeted Immunotherapy against Adenocarcinoma Cells with Nanoparticles Modified by CD16 and MUC1 Aptamers

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Lianyuan Yu ◽  
Yan Hu ◽  
Jinhong Duan ◽  
Xian-Da Yang
Keyword(s):  
Nk Cells ◽  
Cancer Cells ◽  
Dark Field ◽  
Negative Control ◽  
Mucin 1 ◽  
Novel Approach ◽  
Adenocarcinoma Cells ◽  
Dark Field Microscopy ◽  
Average Size ◽  
Nk Cytotoxicity

Mucin 1 (MUC1) is a potentially important target of cancer therapy, being a glycoprotein that is overexpressed on cell surface of many types of adenocarcinomas, including breast, ovarian, colon, lung, and prostatic cancers. Several MUC1-targeted drug delivery systems have been developed and reported, but mobilizing natural killer cells (NK) to fight against MUC1-positive tumor has not been attempted. In this study, we introduced a novel amphipathic nanoparticle (NP) for enhancing the NK cytotoxicity to MUC1-positive cancer cells. The amphipathic NP had CD16 and MUC1 aptamers on its surface and was designed to bind with both the CD16-positive NK cells and the MUC1-positive tumor cells and pull the two types of cells close to each other. The fabricated amphipathic NP had an average size of 574 nm. The aptamers’ conjugation with the NP was confirmed by DNA hybridization experiments. Dark-field microscopy revealed that the amphipathic NP could recruit more NK cells to the vicinity of MUC1-positive cancer cells. Additionally, the amphipathic NP significantly enhanced the NK cytotoxicity to MUC1-positive cancer cellsp<0.01, but not that to the MUC1-negative control cells. The results suggest that NK cells may potentially be mobilized to selectively fight against MUC1-positive cancer cells.

scholarly journals The Effect of Compound Sophora on Fluorouracil and Oxaliplatin Resistance in Colorectal Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
WeiHua Yin ◽  
GuPing Zhong ◽  
HuiZhen Fan ◽  
HongMei Xia
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Sw480 Cell ◽  
Gastric Cancer Cells ◽  
Glycoprotein P ◽  
Chemotherapy Drugs ◽  
Protein Levels ◽  
Enhanced Expression

Fluorouracil (5-FU) and oxaliplatin (L-OHP) are the most commonly used chemotherapy drugs for colorectal cancer, though resistance is common. Compound Sophora injection is a traditional Chinese medicine that can protect the liver against oxidation, improve immunity, and enhance sensitivity to chemotherapy; it may have an effect of reversing resistance in 5-FU- and L-OHP-resistant gastric cancer cells (5-FU/SW480 and L-OHP/SW480, respectively). A concentration gradient experiment was performed to identify a nontoxic dose of compound Sophora injection. 5-FU/SW480 and L-OHP/SW480 cells were treated with the nontoxic dose of compound radix Sophorae injection for 48 h, and changes in drug resistance to 5-FU and L-OHP were detected. Alterations in apoptosis and the cell cycle were assessed, as were the mRNA and protein levels of permeability glycoprotein (P-gp), annexin A1 (ANXA1), and ATP-binding cassette superfamily G member 2 (ABCG2). Flow cytometry showed a reduction in the number of cells in the G1 phase and an increase of cells in the S phase (P<0.05). mRNA and protein expression of P-gp and ABCG2 was significantly higher in 5-FU/SW480 and L-OHP/SW480 cell lines, and ANXA1 expression decreased significantly (P<0.05). Compound Sophora injection can reverse the drug resistance of 5-FU/SW480 and L-OHP/SW480 cell lines to 5-FU and L-OHP, respectively, possibly through a mechanism involving reduced expression of P-gp and ABCG2 but enhanced expression of ANXA1, which is the basis for the identification of clinical drug resistance in colorectal cancer.

scholarly journals Mucin 1 regulates the hypoxia response in head and neck cancer cells

2021 ◽  
Vol 147 (4) ◽  
pp. 331-339
Author(s):  
Kusumawadee Utispan ◽  
Sittichai Koontongkaew
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Cancer Cells ◽  
Neck Cancer ◽  
Mucin 1 ◽  
Hypoxia Response

N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene), a chemopotentiating agent with hormetic effects on DNA synthesis in vitro, may improve survival in patients with metastatic breast cancer

2008 ◽  
Vol 27 (2) ◽  
pp. 143-147 ◽  
Author(s):  
Lorne J Brandes
Keyword(s):  
Breast Cancer ◽  
Dna Synthesis ◽  
Cancer Cells ◽  
Multiple Drug Resistance ◽  
Metastatic Breast ◽  
Chemotherapeutic Agents ◽  
Multiple Drug ◽  
Glycoprotein P ◽  
Hormetic Effect

N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene) is a novel anti-histaminic and chemopotentiating agent that has a hormetic effect on DNA synthesis in MCF (Michigan Cancer Foundation)-7 human breast cancer cells in vitro and stimulates the growth of experimental tumors in rodents. In a prospectively randomized phase three trial (NCIC MA.19), 152 patients who were co-administered DPPE and doxorubicin survived 50% longer ( P < 0.03) than 153 patients who were administered the same dose and schedule of doxorubicin alone. At clinically relevant in vitro concentrations that do not inhibit the P-glycoprotein (P-gp) pump, DPPE selectively sensitizes the cancer cells that express the multiple drug resistance phenotype, making them more susceptible to the cytotoxic effects of chemotherapeutic agents, including anthracyclines and taxanes. Based on its previously demonstrated interaction with histamine at CYP3A4, a P450 that metabolizes arachidonic acid, and its induction of high levels of prostacyclin in the gut of rodents, modulation by DPPE of the intracellular concentration of arachidonate products, such as hydroxyeicosatetraeinoic acids, implicated in increased cancer cell proliferation and metastasis, is postulated.

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