A nanotechnology-based new approach in the treatment of breast cancer: Biosynthesized silver nanoparticles using Cuminum cyminum L. seed extract

https://doi.org/10.1016/j.jphotobiol.2020.111902Get rights and content

Highlights

  • AgNPs and Bio-AgNPs demonstrated significant anticancer activities on MCF-7 and AU565 cells.

  • Bio-AgNPs were found to be less toxic against J774 macrophage cells in contrast to AgNPs.

  • At non-toxic concentrations applied, anticancer performance of Bio-AgNPs was superior than AgNPs.

  • Both formulation killed more than 85% of breast cancer cells when they were applied at high concentrations.

  • Bio-AgNPs could lead to development of new nanobiotechnological treatment alternatives against breast cancer.

Abstract

The present study reports the anticancer activities of Cuminum cyminum L. (Cumin) seed extract, chemically synthetized silver nanoparticles (AgNPs) and biosynthesized silver nanoparticles (Bio-AgNPs) from Cumin seeds on human breast adenocarcinoma cell line (MCF-7) and human breast adenocarcinoma metastatic cell line (AU565). The synthetized nanoparticles were characterized by dynamic light scattering (DLS), UV–visible spectroscopy (UV–Vis), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and Scanning electron microscopy (SEM). The cytotoxic and anticancer effects of AgNPs and Bio-AgNPs were determined by MTT assay. According to the cytotoxicity analysis, Bio-AgNPs appears to be less toxic against J774 macrophage cells than AgNPs since IC50 values were measured as 0.75 and 1.25 μg/ml for AgNPs and Bio-AgNPs, respectively. On the other hand, Bio-AgNPs demonstrated significant inhibitory effects on human breast cancer cells at non-toxic concentrations such as 0.25 and 0.5 μg/ml. However, at increased concentrations, the lethal effects of AgNPs on breast cancer cells were higher than Bio-AgNPs. When cytotoxic and anticancer characteristics of Cumin extract were investigated, it was established that it did not show any inhibitory effect on J774 cells, while killing the half of MCF-7 cells at investigated concentrations. Interestingly, Cumin extract gave rise to no inhibitory effects against AU565 cells. On the other hand, AgNPs and Bio-AgNPs exhibited considerable anticancer activities on both cell lines. The inhibition percentages of AgNPs on MCF-7 and AU565 cell lines were respectively evaluated as 95% and 97% at the highest concentrations applied (12.5 μg/ml). Similarly, we determined that 87.5% and 96% of MCF-7 and AU565 cells were respectively inhibited when they were exposed to the highest concentrations of Bio-AgNPs. Considering relatively toxic-free features of Bio-AgNPs prepared from Cuminum cyminum L. seed extracts, it can be thought that this formulation will be a pioneer in development of nanotechnology-based new anticancer drug for the treatment of breast cancer in near future.

Introduction

Cancer is broadly referred as to uncontrollable division and aberrant growth of cells. It is one of the biggest global health problems and found in the third place among the other diseases in regards to mortality rates [1,2]. In every year approximately ten million new cases are reported and more than six millions of these are terminated with death [3,4]. Breast cancer is one of the most frequently diagnosed cancer types worldwide. According to World Health Organization (WHO), It is globally influencing more than 2 million women in every year and it is predicted that approximately 650.000 breast cancer patients lose their lives annually. This value nearly corresponds to 15% of all cancer deaths in women and that means breast cancer is the most deathful cancer type among women. The basis of the breast cancer treatment relies on conventional methods such as surgery, chemotherapy and radiotherapy [[5], [6], [7], [8]]. However, these therapies do not always yield the expected results. It is known that applications of conventional anticancer drugs demonstrate significant cytotoxic features not only in cancer cells but also in somatic cells. Furthermore, tumor cells have recently evolved notable chemoresistance against anticancer drugs applied in treatment leading to failure of the therapy. Additionally low cellular uptake, decreased specificity and severe side effects are other considerable limitations of traditional chemotherapeutic agents [[9], [10], [11]]. Moreover, emergence of metastasis that means the spread of cancer cells to other organs of body is another crucial factor decreasing the success of the treatment [12]. Due to serious drawbacks of conventional anticancer therapies, there is a huge neccessity to develop new approaches that would be further utilized for the treatment of breast cancer [[13], [14], [15]].

Nowadays the advancements in nanotechnology provide broad opportunities for development of new diagnostic and treatment approaches against various diseases. Nano-sized materials and devices have been recently utilized in biomedical and pharmaceutical practices like drug delivery, tissue engineering, monitoring and vaccine development. Nanoparticles are believed to demonstrate superior physical, mechanical, chemical and optical properties in contrast to bulk materials [[16], [17], [18]]. Due to their ultra-small dimensions, large surface/volume ratios and suitability for surface modifications, nanoparticles are accepted as promising alternatives to traditional treatment options [[19], [20], [21]]. Recent studies suggest that metallic nanoparticles such as silver, titanium, zinc, gold and iron can be successfully used in treatment of several diseases including cancer. In several studies, it was repeatedly exhibited that metallic nanoparticles had considerable antibacterial, antifungal, antiviral, antidiabetic and anticancer efficacies [22,23]. Among other metallic nanoparticles, use of silver nanoparticles (AgNPs) is reported to be more advantageous, as they are relatively less-toxic, environmentally safe and have extremely large surface areas to interact strongly with cellular membranes. These facilities are believed to improve their biological activities. There are various techniques such as chemical, biochemical and physical methods that are used in the synthesis of AgNPs [24,25]. Many studies indicated in vitro anticancer effects of chemically synthesized AgNPs on both human and animal cancer cell lines [26,27]. On the contrary, in various studies it has been also shown that chemically synthetized AgNPs were toxic against normal cell lines although they exhibited significant anticancer effects. The possible reason for the cytotoxicities of chemically synthetized AgNPs is the use of toxic solvents, synthetic-chemical reducing agents and stabilizers during synthesis process [[28], [29], [30]]. Therefore, in recent years researches have mainly focused on decreasing cyotoxicity of silver nanoparticles in order to remove the limitations preventing their use in clinical trials.

Accordingly, green nanotechnology approaches are getting more and more important with increasing awareness about a safe and clean environment. Green synthesized nanoparticles have many advantages such as non-toxicity, high stability, being safely and eco-friendly, low aggregation properties and brilliant anticancer /antioxidant features that make them preferable for medical applications [[31], [32], [33], [34]]. Furthermore, it is known that green-synthetized nanoparticles displayed very strong antimicrobial performances since their significant lethal effects were proven against several bacteria, viruses, parasites, molds and yeasts in various studies [[35], [36], [37], [38]]. Biogenic nanoparticles can be isolated from different biological sources such as bacteria, fungi and plants [[39], [40], [41], [42], [43]]. Biological agents that are existed in these sources are known to exhibit very important reductive and stabilizing properties in the synthesis of AgNPs. Therefore, use of these biological agents contribute the fabrication of less-toxic and eco-friendly AgNPs in contrast to traditional chemical and physical methods [[44], [45], [46], [47], [48], [49]].

Today, various plant sources are used in the synthesis of green nanoparticles. Researchers benefit from the seed and leaf extracts of plants as stabilizing agents for production of biogenic nanoparticles. The biological activities of green nanoparticles accurately depend on the types of the plant from which the extracts are prepared and the abundancy of anti-microbial/anti-carcinogenic compounds which the plant contains [50,51]. However, studies on investigating the anticarcinogenic effects of plant based green nanoparticles on breast cancer are very limited and insufficient [52]. In one study, green AgNPs synthetized from Lippia nodiflora antennas were examined for their anticancer efficacies at different concentrations on breast cancer cells. The results revealed that the inhibitory percentage of green nanoparticles on cancer cells was about 72.8% at the concentration of 100 μg / ml [53]. In another study, Selvi et al. found that green AgNPs synthesized by Padina tetrastromatica had cytotoxic effects on MCF-7 cells at high concentrations applied such as 100 and 200 μg / ml [54].

In the literature there are also some studies based on green nanoparticles synthetized from Cuminum cyminum L. (Cumin) extract investigating their biological activities. Cumin is the most widely used spice type in food products in Asia. The major components of Cumin oil are cuminaldehyde, cemene and terpenoids [55]. Some researchers have determined that some of the major active ingredients in cumin oil such as cuminal and chimeric alcohol demonstrated very strong anticancer effects on particularly colon and lung cancers [56,57]. However, in the literature we have not found any study examining anticancer efficacies of silver nanoparticles synthesized with Cumin extract against breast cancer cell lines. Therefore, purpose of the present study was to synthetize green nanoparticles from Cuminum cyminum L. seed extract, characterize prepared nanoparticles with various methods and investigate their in vitro anticancer activities on different human breast cancer cell lines such as MCF-7 and AU565 in comparison with chemically synthetized nanoparticles.

Section snippets

Materials

Cuminum cyminum L. seeds were a gift from Azerbaijan Medical University. Silver nitrate>99%, fetal bovine serum (FBS), medium DMEM-H and RPMI-1640, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), Dimethyl sulfoxide (DMSO), Trypsin-EDTA, penicillin-streptomycin solution, were all purchased from Sigma-Aldrich. All the aqueous solutions were prepared with milli-Q water.

Preparation of Aqueous Cuminum cyminum L. Seed Extracts

20 g of Cumin seed was washed with distilled water, pounded and placed into a water bath at 90 °C for

UV–Vis Spectrum Analysis

The synthesis of AgNPs is very sensitive and the success in the synthesis of nanoparticles mostly depends on some important parameters such as the reaction time, the concentration of AgNO3, the volume of the extract and the reaction temperature. The reduction of Ag+ ions to Ag0 by Cuminum cyminum L. extract was determined with a UV–Vis spectrophotometer by recording the absorption as a function of time. Fig. 1 shows the UV–Vis spectra of biosynthesized silver nanoparticles at different time

Discussion

For the first time in this study the anticancer effect of Cumin extract, AgNPs, and Bio-AgNPs was comparatively examined on MCF-7 and AU565 human breast cancer cell lines. It was determined that both AgNPs and Bio-AgNPs demonstrated excellent anticancer efficacy on each cancer type since they considerably diminished cellular viability values of cancer cells in contrast to control group. Furthermore, we also analyzed cytotoxic activities of applied formulations and found that Bio-AgNPs were less

Conclusion

This study confirmed Cuminum cyminum L. seed extract could be used as stabilizer and reductive agent in the biogenic synthesis of silver nanoparticles. UV–visible spectroscopy, XRD, EDS, SEM, FTIR techniques were used to characterize the Cumin extract, AgNPs, and Bio-AgNPs. Anticancer activity of the Bio-AgNPs from Cuminum cyminum L. seed extract was investigated for the first time on different human breast cancer cell lines (MCF-7 and AU565). The obtained results demonstrated that Cumin-AgNPs

Funding

This study was supported by Yildiz Technical University Scientific Research Project Coordinatorship with the project number of 2027.

Declaration of Competing Interest

The authors declare that they have no conflict of interest.

Acknowledgements

Authors are thankful to the Yildiz Technical University for their financial support with project ID 2027 and Yeditepe University Genetic and Bioengineering Department for providing AU565 cell line.

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