Influence of bismuth oxide nanoparticles on bystander effects in MCF-7 and hFOB 1.19 cells under 10 MV photon beam irradiation
Introduction
Radiotherapy is always recommended as the primary treatment of choice for cancer disease because of their superior clinical outcome compared to surgery, chemotherapy and the other alternative treatment. The advantage of radiotherapy over other treatment choices owing to better survival, local control, and profiles of quality of life or toxicity (Rosenblatt et al., 2018). However, irradiation of cancer cells may also affect the nearby normal cells in which could increase the risk of secondary cancer in the future. In an effort to improve the efficacy of cancer treatment, nanomaterials have been introduced to increase radiotoxicity to the cancerous region and minimize the biological effect on normal cells (Song et al., 2013). Extensive investigations have been carried out by researchers regarding enhancement of radiation toxicity on the targeted tumor cells through the application of radiosensitizer. The use of radiosensitizer such as gold nanoparticles (AuNPs), iron oxide nanoparticles (Fe3O4 NPs), platinum nanodendrites (PtNDs) and bismuth oxide nanoparticles (Bi2O3 NPs) have been reported as radiosensitizer that able to increase the effect of radiotherapy to cancerous area (Abidin et al., 2019; Khoshgard et al., 2017; Muhammad et al., 2018; Rahman et al., 2019, 2009; Rashid et al., 2018).
The existence of metallic nanoparticles within the cell produces a greater amount of secondary electrons from the radiation interactions. In consequences, increases in free radical numbers will contribute to deoxyribonucleic acid (DNA) molecules damages and cells death (Rahman et al., 2009). The biological effects of ionizing radiation were believed to be restricted to tissues within the treatment field due to direct targeting to the nucleus in which leading to DNA damage. Recently, attention in radiobiological studies has been widen to non-targeted effects of adjacent tissue surrounded the targeted area. The response of the non-irradiated cells to the radiation exposure is known as radiation-induced bystander effects (RIBE) (Marín et al., 2015). Bystander effects describe a situation where cells that have not been directly exposed to ionizing radiation behave as they though they have been exposed. As a result, the cells were killed or show chromosomal instability and other abnormalities (Mothersill and Seymour, 2004). RIBE in cells have been widely observed in radiobiology. Cells that are exposed to bystander signals can experience adverse effects including cell killing, the induction of micronuclei (MN), sister chromatid exchanges, mutations, genomic instability, changes in gene expression, decreases in cell proliferation and survival, changes in cell growth and cell death (Luo et al., 2018; Mothersill and Seymour, 2003; Shao et al., 2005). The RIBE may occurs through the transmitted signals from irradiated cells either by direct cell-to-cell contacts or by secretion of soluble factors into the medium (Rostami et al., 2016).
RIBE mainly expand the radiotoxicity effects to the non-targeted area. The application of radiosensitizer during the treatment rise up the issue if they could contribute to the RIBE in non-irradiated cells. Despite some promising investigations on RIBE, there are still gaps in understanding the mechanism and responses between the irradiated cells and adjacent healthy cells when radiosensitizer is applied during radiation treatment. Bystander effects may play an important role in radiotherapy. Understanding the bystander effects can improve radiobiological modelling of targeted tumor and minimizing the effect to healthy tissue (Zhang et al., 2016). The present in vitro study intended to examine the possibility of increment in RIBE as a result of Bi2O3 NPs application during radiotherapy for 10 MV photon beam. The RIBE responses between the normal and cancerous cells after the incubation with irradiated cell conditioned medium (ICCM) were also investigated.
Section snippets
Cell culture
MCF-7, human breast cancer cells line, and hFOB 1.19, human fetal osteoblast cell lines were used in the experiments. Cells were grown in tissue culture flask containing Dulbecco's modified Eagle's medium (DMEM) (Nacalai Tesque, Kyoto, Japan) which is supplemented with 10% fetal bovine serum and 1% antibiotics (10,000 units/mL penicillin and 10,000 μg/mL streptomycin) (Nacalai Tesque, Kyoto, Japan) in humidified atmosphere of 5% CO2 at 37°C. The stock cell cultures were maintained in
Cytotoxicity of Bi2O3
Human breast cancer cells MCF-7 and normal osteoblast hFOB 1.19 cell lines were treated with various concentrations of Bi2O3 (0–50 μMol/L) for 48 h. The effect of Bi2O3 NPs on cell viability was evaluated by PrestoBlue assay. Our results presented no signs of cytotoxicity in both cells when incubated with all concentration of Bi2O3 NPs for 48 h compared to untreated control cells (Fig. 1). Both treated cells were able to proliferate for more than 80% after 48 h exposures to Bi2O3 NPs at
Discussion
Several studies have been conducted to test the efficacy of Bi2O3 NPs as a radiosensitizer to enhance the effectiveness of radiation treatment (Abidin et al., 2019; Sisin et al., 2019; Stewart et al., 2016). However, its role in the bystander effect of radiation therapy has not yet been determined. To our knowledge, this is the first precedent to explore the consequence of Bi2O3 NPs in response to bystander effects of radiation.
The effect of nanomaterials is highly related to the
Conclusion
The present work provided the first in vitro study of the Bi2O3 NPs on the bystander effects in the non-targeted cells through medium transfer technique. In particular, to ensure the presence of radiosensitizer does not neutralized the therapeutic ratio, it is necessary to analyse the effect of Bi2O3 NPs on RIBE. Interestingly, our study demonstrates that the Bi2O3 NPs do not contribute and enhance the RIBE in both cancer and normal cells.
CRediT authorship contribution statement
Nur Hamizah Mohd Zainudin: Methodology, Investigation, Writing - original draft. Khairunisak Ab Razak: Resources, Investigation. Safri Zainal Abidin: Investigation. Reduan Abdullah: Investigation. Wan Nordiana Rahman: Conceptualization, Methodology, Writing - review & editing, Investigation, Supervision, Funding acquisition.
Declaration of competing interest
The authors declare that they have no known competing interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgement
This work was supported by Universiti Sains Malaysia Research University Grant (RUI:1001/PPSK/8012212).
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