Structure of human cortisol-producing cytochrome P450 11B1 bound to the breast cancer drug fadrozole provides insights for drug design

Backgorund: Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively used for targeted drug delivery systems due to their unique magnetic properties. Objective: In this study, it’s aimed to develop a novel targeted 99mTc radiolabeled polymeric drug delivery system for Gemcitabine (GEM). Methods: Gemcitabine, an anticancer agent, was encapsulated into polymer nanoparticles (PLGA) together with iron oxide nanoparticles via double emulsion technique and then labeled with 99mTc. SPIONs were synthesized by reduction–coprecipitation method and encapsulated with oleic acid for surface modification. Size distribution and the morphology of the synthesized nanoparticles were caharacterized by dynamic light scattering(DLS)and scanning electron microscopy(SEM), respectively. Radiolabeling yield of SPION-PLGAGEM nanoparticles were determined via Thin Layer Radio Chromatography (TLRC). Cytotoxicity of GEM loaded SPION-PLGA were investigated on MDA-MB-231 and MCF7 breast cancer cells in vitro. Results: SEM images displayed that the average size of the drug-free nanoparticles was 40 nm and the size of the drug-loaded nanoparticles was 50 nm. The diameter of nanoparticles were determined as 366.6 nm by DLS, while zeta potential was found as-29 mV. SPION was successfully coated with PLGA, which was confirmed by FTIR. GEM encapsulation efficiency of SPION-PLGA was calculated as 4±0.16 % by means of HPLC. Radiolabeling yield of SPION-PLGA-GEM nanoparticles were determined as 97.8±1.75 % via TLRC. Cytotoxicity of GEM loaded SPION-PLGA were investigated on MDA-MB-231 and MCF7 breast cancer cells. SPION-PLGA-GEM showed high uptake on MCF-7, whilst incorporation rate was increased for both cell lines which external magnetic field application. Conclusion: 99mTc labeled SPION-PLGA nanoparticles loaded with GEM may overcome some of the obstacles in anti-cancer drug delivery because of their appropriate size, non-toxic, and supermagnetic characteristics.

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Clinical applications of circulating tumor DNA in monitoring breast cancer drug resistance

Future Oncology ◽

10.2217/fon-2019-0760 ◽

2020 ◽

Vol 16 (34) ◽

pp. 2863-2878

Author(s):

Yang Liu ◽

Qian Du ◽

Dan Sun ◽

Ruiying Han ◽

Mengmeng Teng ◽

...

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Digital Pcr ◽

Circulating Tumor Dna ◽

Resistance Mechanisms ◽

Clinical Applications ◽

Current Status ◽

Cancer Drug ◽

Genomic Alteration ◽

Tumor Dna

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide. Unfortunately, treatments often fail because of the development of drug resistance, the underlying mechanisms of which remain unclear. Circulating tumor DNA (ctDNA) is free DNA released into the blood by necrosis, apoptosis or direct secretion by tumor cells. In contrast to repeated, highly invasive tumor biopsies, ctDNA reflects all molecular alterations of tumors dynamically and captures both spatial and temporal tumor heterogeneity. Highly sensitive technologies, including personalized digital PCR and deep sequencing, make it possible to monitor response to therapies, predict drug resistance and tailor treatment regimens by identifying the genomic alteration profile of ctDNA, thereby achieving precision medicine. This review focuses on the current status of ctDNA biology, the technologies used to detect ctDNA and the potential clinical applications of identifying drug resistance mechanisms by detecting tumor-specific genomic alterations in breast cancer.

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Glycyrrhiza glabra extract and quercetin reverses cisplatin resistance in triple-negative MDA-MB-468 breast cancer cells via inhibition of cytochrome P450 1B1 enzyme

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2017.11.013 ◽

2017 ◽

Vol 27 (24) ◽

pp. 5400-5403 ◽

Cited By ~ 12

Author(s):

Rajni Sharma ◽

Linda Gatchie ◽

Ibidapo S. Williams ◽

Shreyans K. Jain ◽

Ram A. Vishwakarma ◽

...

Keyword(s):

Breast Cancer ◽

Cytochrome P450 ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Triple Negative ◽

Cisplatin Resistance ◽

Glycyrrhiza Glabra ◽

Cytochrome P450 1B1

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Intratumoural Cytochrome P450 Expression in Breast Cancer: Impact on Standard of Care Treatment and New Efforts to Develop Tumour-Selective Therapies

Biomedicines ◽

10.3390/biomedicines9030290 ◽

2021 ◽

Vol 9 (3) ◽

pp. 290

Author(s):

Smarakan Sneha ◽

Simon C. Baker ◽

Andrew Green ◽

Sarah Storr ◽

Radhika Aiyappa ◽

...

Keyword(s):

Breast Cancer ◽

Cytochrome P450 ◽

Treatment Strategies ◽

Standard Of Care ◽

Therapeutic Index ◽

Cancer Cell Proliferation ◽

Selective Treatment ◽

Standard Of Care Treatment ◽

Future Work ◽

Treat Breast Cancer

Despite significant advances in treatment strategies over the past decade, selective treatment of breast cancer with limited side-effects still remains a great challenge. The cytochrome P450 (CYP) family of enzymes contribute to cancer cell proliferation, cell signaling and drug metabolism with implications for treatment outcomes. A clearer understanding of CYP expression is important in the pathogenesis of breast cancer as several isoforms play critical roles in metabolising steroid hormones and xenobiotics that contribute to the genesis of breast cancer. The purpose of this review is to provide an update on how the presence of CYPs impacts on standard of care (SoC) drugs used to treat breast cancer as well as discuss opportunities to exploit CYP expression for therapeutic intervention. Finally, we provide our thoughts on future work in CYP research with the aim of supporting ongoing efforts to develop drugs with improved therapeutic index for patient benefit.

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