Toxicity Mechanism of Gadolinium Oxide Nanoparticles and Gadolinium Ions in Human Breast Cancer Cells

2019 ◽  
Vol 20 (11) ◽  
pp. 907-917 ◽  
Author(s):  
Mohd Javed Akhtar ◽  
Maqusood Ahamed ◽  
Hisham Alhadlaq ◽  
Salman Alrokayan
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cell Membrane ◽  
Oxidative Damage ◽  
Human Breast Cancer ◽  
Membrane Damage ◽  
Gadolinium Oxide ◽  
Human Breast ◽  
Mechanisms Of Toxicity

Background: Due to the potential advantages of Gadolinium Nanoparticles (NPs) over gadolinium elements, gadolinium based NPs are currently being explored in the field of MRI. Either in elemental form or nanoparticulate form, gadolinium toxicity is believed to occur due to the deposition of gadolinium ion (designated as Gd3+ ion or simply G ion). Objective: There is a serious lack of literature on the mechanisms of toxicity caused by either gadolinium-based NPs or ions. Breast cancer tumors are often subjected to MRIs, therefore, human breast cancer (MCF-7) cells could serve as an appropriate in vitro model for the study of Gadolinium Oxide (GO) NP and G ion. Methods: Cytotoxicity and oxidative damage was determined by quantifying cell viability, cell membrane damage, and Reactive Oxygen Species (ROS). Intracellular Glutathione (GSH) was measured along with cellular Total Antioxidant Capacity (TAC). Autophagy was determined by using Monodansylcadaverine (MDC) and Lysotracker Red (LTR) dyes in tandem. Mitochondrial Membrane Potential (MMP) was measured by JC-1 fluorescence. Physicochemical properties of GO NPs were characterized by field emission transmission electron microscopy, X-ray diffraction, and energy dispersive spectrum. Results: A time- and concentration-dependent toxicity and oxidative damage was observed due to GO NPs and G ions. Bax/Bcl2 ratios, FITC-7AAD double staining, and cell membrane blebbing in phase-contrast images all suggested different modes of cell death induced by NPs and ions. Conclusion: In summary, cell death induced by GO NPs with high aspect ratio favored apoptosis-independent cell death, whereas G ions favored apoptosis-dependent cell death.

scholarly journals GDC-0941, a Novel Class I Selective PI3K Inhibitor, Enhances the Efficacy of Docetaxel in Human Breast Cancer Models by Increasing Cell Death In Vitro and In Vivo

2012 ◽  
Vol 18 (14) ◽  
pp. 3901-3911 ◽  
Author(s):  
Jeffrey J. Wallin ◽  
Jane Guan ◽  
Wei Wei Prior ◽  
Leslie B. Lee ◽  
Leanne Berry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Human Breast Cancer ◽  
Pi3k Inhibitor ◽  
Class I ◽  
Human Breast ◽  
Cancer Models

scholarly journals Breast Cancer Cryoablation: Assessment of the Impact of Fundamental Procedural Variables in an In Vitro Human Breast Cancer Model

2020 ◽  
Vol 14 ◽  
pp. 117822342097236
Author(s):  
Kristi K Snyder ◽  
Robert G Van Buskirk ◽  
John G Baust ◽  
John M Baust
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Human Breast Cancer ◽  
Human Breast ◽  
Freeze Thaw ◽  
Thaw Cycle ◽  
Freeze Thaw Cycle ◽  
The Impact ◽  
Mcf 7

Introduction: Breast cancer is the most prominent form of cancer and the second leading cause of death in women behind lung cancer. The primary modes of treatment today include surgical excision (lumpectomy, mastectomy), radiation, chemoablation, anti-HER2/neu therapy, and/or hormone therapy. The severe side effects associated with these therapies suggest a minimally invasive therapy with fewer quality of life issues would be advantageous for treatment of this pervasive disease. Cryoablation has been used in the treatment of other cancers, including prostate, skin, and cervical, for decades and has been shown to be a successful minimally invasive therapeutic option. To this end, the use of cryotherapy for the treatment of breast cancer has increased over the last several years. Although successful, one of the challenges in cryoablation is management of cancer destruction in the periphery of the ice ball as the tissue within this outer margin may not experience ablative temperatures. In breast cancer, this is of concern due to the lobular nature of the tumors. As such, in this study, we investigated the level of cell death at various temperatures associated with the margin of a cryogenic lesion as well as the impact of repetitive freezing and thawing methods on overall efficacy. Methods: Human breast cancer cells, MCF-7, were exposed to temperatures of −5°C, −10°C, −15°C, −20°C, or −25°C for 5-minute freeze intervals in a single or repeat freeze-thaw cycle. Samples were thawed with either passive or active warming for 5 or 10 minutes. Samples were assessed at 1, 2, and 3 days post-freeze to assess cell survival and recovery. In addition, the modes of cell death associated with freezing were assessed over the initial 24-hour post-thaw recovery period. Results: Exposure of MCF-7 cells to −5°C and −10°C resulted in minimal cell death regardless of the freeze/thaw conditions. Freezing to a temperature of −25°C resulted in complete cell death 1 day post-thaw with no cell recovery in all freeze/thaw scenarios evaluated. Exposure to a single freeze event resulted in a gradual increase in cell death at −15°C and −20°C. Application of a repeat freeze-thaw cycle (dual 5-minute freeze) resulted in an increase in cell death with complete destruction at −20°C and near complete death at −15°C (day 1 survival: single −15°C freeze/thaw = 20%; repeated −15°C freeze/thaw = 4%). Analysis of thaw interval time (5 vs 10 minute) demonstrated that the shorter 5-minute thaw interval between freezes resulted in increased cell destruction. Furthermore, investigation of thaw rate (active vs passive thawing) demonstrated that active thawing resulted in increased cell survival thereby less effective ablation compared with passive thawing (eg, −15°C 5/10/5 procedure survival, passive thaw: 4% vs active thaw: 29%). Conclusions: In summary, these in vitro findings suggest that freezing to temperatures of 25°C results in a high degree of breast cancer cell destruction. Furthermore, the data demonstrate that the application of a repeat freeze procedure with a passive 5-minute or 10-minute thaw interval between freeze cycles increases the minimal lethal temperature to the −15°C to −20°C range. The data also demonstrate that the use of an active thawing procedure between freezes reduces ablation efficacy at temperatures associated with the iceball periphery. These findings may be important to improving future clinical applications of cryoablation for the treatment of breast cancer.

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