scholarly journals Gamma Tocopherol Reduced Chemotherapeutic-Induced ROS in an Ovarian Granulosa Cell Line, But Not in Breast Cancer Cell Lines In Vitro

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 51 ◽  
Author(s):  
Daniela Figueroa Gonzalez ◽  
Fiona Young

Doxorubicin and cyclophosphamide are used to treat breast cancer, but they also cause infertility through off-target cytotoxicity towards proliferating granulosa cells that surround eggs. Each chemotherapeutic generates reactive oxygen species (ROS) but the effects of the combination, or the antioxidants alpha (αToc) and gamma tocopherol (γToc) on ROS in breast cancer or ovarian cells are unknown. Human breast cancer (MCF7, T47D) and ovarian cancer (OVCAR, COV434) cells were loaded with DCDFA and exposed (1, 2, 3, 24 h) to the MCF7-derived EC25 values of individual agents, or to combinations of these. ROS were quantified and viable cells enumerated using crystal violet or DAPI. Each chemotherapeutic killed ~25% of MCF7, T47D and OVCAR cells, but 57 ± 2% (doxorubicin) and 66 ± 2% (cyclophosphamide) of the COV434 granulosa cells. The combined chemotherapeutics decreased COV434 cell viability to 34 ± 5% of control whereas doxorubicin + cyclophosphamide + γToc reduced ROS within 3 h (p < 0.01) and reduced cytotoxicity to 54 ± 4% (p < 0.05). αToc was not cytotoxic, whereas γToc killed ~25% of the breast cancer but none of the ovarian cells. Adding γToc to the combined chemotherapeutics did not change ROS or cytotoxicity in MCF7, T47D or OVCAR cells. The protection γToc afforded COV434 granulosa cells against chemotherapy-induced ROS and cytotoxicity suggests potential for fertility preservation.

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4332
Author(s):  
Nurul Izzati Zulkifli ◽  
Musthahimah Muhamad ◽  
Nur Nadhirah Mohamad Zain ◽  
Wen-Nee Tan ◽  
Noorfatimah Yahaya ◽  
...  

A bottom-up approach for synthesizing silver nanoparticles (AgNPs-GA) phytomediated by Garcinia atroviridis leaf extract is described. Under optimized conditions, the AgNPs-GA were synthesized at a concentration of 0.1 M silver salt and 10% (w/v) leaf extract, 1:4 mixing ratio of reactants, pH 3, temperature 32 °C and 72 h reaction time. The AgNPs-GA were characterized by various analytical techniques and their size was determined to be 5–30 nm. FTIR spectroscopy indicates the role of phenolic functional groups in the reduction of silver ions into AgNPs-GA and in supporting their subsequent stability. The UV-Visible spectrum showed an absorption peak at 450 nm which reflects the surface plasmon resonance (SPR) of AgNPs-GA and further supports the stability of these biosynthesized nanoparticles. SEM, TEM and XRD diffractogram analyses indicate that AgNPs-GA were spherical and face-centered-cubic in shape. This study also describes the efficacy of biosynthesized AgNPs-GA as anti-proliferative agent against human breast cancer cell lines, MCF-7 and MCF-7/TAMR-1. Our findings indicate that AgNPs-GA possess significant anti-proliferative effects against both the MCF-7 and MCF-7/TAMR-1 cell lines, with inhibitory concentration at 50% (IC50 values) of 2.0 and 34.0 µg/mL, respectively, after 72 h of treatment. An induction of apoptosis was evidenced by flow cytometry using Annexin V-FITC and propidium iodide staining. Therefore, AgNPs-GA exhibited its anti-proliferative activity via apoptosis on MCF-7 and MCF-7/TAMR-1 breast cancer cells in vitro. Taken together, the leaf extract from Garcinia atroviridis was found to be highly capable of producing AgNPs-GA with favourable physicochemical and biological properties.


Author(s):  
Philippa D. Darbre ◽  
Roger J. Daly

SynopsisOestrogen regulates the growth of human breast cancer cell lines ZR-75–1, T-47-D and MCF-7 (KO and McGrath). Basal cell growth can be reduced (T-47-D) or eliminated (ZR-75–1) by prior growth in the absence of steroid and phenol red for three weeks, demonstrating that oestrogens can have long-lasting effects on cells in culture (termed “steroid memory”). Effects of oestradiol on different cell biological parameters are described and interaction with other steroids and serum growth factors is discussed. Antioestrogen action in these cell lines is affected by at least five parameters: (1) presence of phenol red, (2) time in culture, (3) cell density, (4) antioestrogen concentration, (5) steroid memory.An in vitro model for loss of oestrogen sensitivity in breast cancer is presented. Both dependent (ZR-75–1) and responsive (T-47-D) cells lose oestrogen sensitivity when deprived of steroid in the long term but show a gradual increase in growth. For ZR-75–1 cells, the effects appear to be clonal but occur at a high frequency (about 1 in 1,000 cells). Parallel alterations in sensitivity to other steroids, antioestrogens and serum growth factors are shown. Molecular markers of this action are described and the results compared with the well-established model for loss of androgen/glucocorticoid sensitivity in SI 15 cells.


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