The comparison of the apoptosis effects of titanium dioxide nanoparticles into MDA-MB-231 cell line in microgravity and gravity conditions

Document Type : Research Paper

Authors

1 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Department of Biotechnology, Iranian Research Organization for Science and Technology, Tehran, Iran

3 Aerospace Research Institute, Ministry of Science Research and Technology, Tehran, Iran

Abstract

Objective (s): Gravity could affect some system features and perform directly as an organizing field factor. Recent investigations have examined the titanium dioxide nanoparticles (TiO2 NPs) in biomedical applications, mostly in the cancer treatment field. This study aimed to evaluate the effects of simulated microgravity combined with TiO2 NPs in MDA-MB-231 cells proliferation for the first time. In other words, this study examined the utility of the microgravity environment in nano-therapy.
Materials and Methods: The MDA-MB-231 human breast cancer cell line and TiO2 NPs were purchased. The 2D clinostat was applied for the simulation of the microgravity. The morphological studies, MTT cytotoxicity assay, Acridine orange/Ethidium bromide double staining studies and flow cytometry analysis were utilized.
Results: The MTT assay, the morphological studies, Acridine orange/Ethidium bromide double staining studies and flow cytometry analysis confirmed the apoptosis-inducing effect of microgravity in combination with TiO2 NPs. The IC50 of simulated microgravity in the presence of TiO2 NPs was determined to be 130 µM. Furthermore, MDA-MB-231 cells exposed to microgravity adopted a different phenotype.
Conclusion: Based on our observation, although the relative mechanisms need to be explored further, microgravity can strictly affect the TiO2 NPs effects on MDA-MB-231 cells. The significance of this study lied in the fact that simulating microgravity can be a powerful physical cure for cancer therapy and open new horizons for the studies in the field of biology, biophysics, and medicine.

Keywords

References

1.Manzano AI, Herranz R, van Loon JJ, Medina FJ. A hypergravity environment induced by centrifugation alters plant cell proliferation and growth in an opposite way to microgravity. Microgravity Sci Technol. 2012; 24(6): 373-381.
2.Blaber E, Sato K, Almeida EA. Stem cell health and tissue regeneration in microgravity. Stem Cells Dev. 2014; 23(S1): 73-78.
3.McPherson A, DeLucas LJ. Microgravity protein crystallization. NPJ Microgravity. 2015; 1: 1-20.
4.Shinde V, Brungs S, Henry M, Wegener L, Nemade H, Rotshteyn T, Acharya A. Baumstark-Khan C. Hellweg C.E. Hescheler J. Hemmersbach R. Sachinidis A. Simulated microgravity modulates differentiation processes of embryonic stem cells. Cell Physiol Biochem. 2016; 38(4): 1483-1499.
5.Buckey JC. Space physiology: Oxford University Press, USA; 2006.
6.Albrecht-Buehler G. Possible mechanisms of indirect gravity sensing by cells. ASGSB Bull. 1991;4(2): 25-34.
7.Furukawa T, Tanimoto K, Fukazawa T, Imura T, Kawahara Y, Yuge L. Simulated microgravity attenuates myogenic differentiation via epigenetic regulations. NPJ Microgravity. 2018; 4: 1-8.
8.Sahana J, Nassef MZ, Wehland M, Kopp S, KrKr Kawahara Y, Yuge L. Decreased E-Cadherin in MCF7 Human Breast Cancer Cells Forming Multicellular Spheroids Exposed to Simulated Microgravity. Proteomics. 2018; 28(3): e1800015.
9.Masiello MG, Cucina A, Proietti S, Palombo A, Coluccia P, D’Anselmi F, Dinicola S, Pasqualato A, Morini V, Bizzarri M. Phenotypic switch induced by simulated microgravity on MDA-MB-231 breast cancer cells. BioMed Res Int. 2014; 2014: 1-12.
10.Vassy J, Portet S, Beil M, Millot G, Fauvel-Lafeve F, Gasset G, Schoevaert D. Weightlessness acts on human breast cancer cell line MCF-7. Adv Space Res. 2003; 32(8): 1595-1603.
11.Qian A, Zhang W, Xie L, Weng Y, Yang P, Wang Z, Hu L, Xu H, Tian Z, Shang P. Simulated weightlessness alters biological characteristics of human breast cancer cell line MCF-7. Acta Astronaut. 2008; 63(7-10): 947-958.
12.Grigoryan E, Anton H, Mitashov V. Real and simulated microgravity can activate signals stimulating cells to enter the S phase during lens regeneration in urodelean amphibians. Adv Space Res. 2006; 38(6): 1071-1078.
13.Yuge L, Kajiume T, Tahara H, Kawahara Y, Umeda C, Yoshimoto R, Wu SL, Yamaoka K, Asashima M, Kataoka K, Ide T. Microgravity potentiates stem cell proliferation while sustaining the capability of differentiation. Stem Cells Dev. 2006; 15(6): 921-929.
14.Jin S, Leach JC, Ye K. Nanoparticle-mediated gene delivery. Micro and Nano Technologies in Bioanalysis: Springer; 2009: 547-557.
15.Lusvardi G, Barani C, Giubertoni F, Paganelli G. Synthesis and Characterization of TiO2 Nanoparticles for the Reduction of Water Pollutants. Materials (Basel). 2017; 10(10): 1-11.
16.Iavicoli I, Leso V, Fontana L, Bergamaschi A. Toxicological effects of titanium dioxide nanoparticles: a review of in vitro mammalian studies. Eur Rev Med Pharmacol Sci. 2011; 15(5): 481-508.
17.Hussain S, Hess K, Gearhart J, Geiss K, Schlager J. In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol In Vitro. 2005; 19(7): 975-983.
18.Lai JC, Lai MB, Jandhyam S, Dukhande VV, Bhushan A, Daniels CK, Leung SW. Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts. Int J Nanomedicine. 2008; 3(4): 533-545.
19.Shukla RK, Kumar A, Gurbani D, Pandey AK, Singh S, Dhawan A. TiO2 nanoparticles induce oxidative DNA damage and apoptosis in human liver cells. Nanotoxicology. 2013; 7(1): 48-60.
20.Hekmat A, Saboury AA, Divsalar A, Seyedarabi A. Structural effects of TiO2 nanoparticles and doxorubicin on DNA and their antiproliferative roles in T47D and MCF7 cells. Anticancer Agents Med Chem. 2013; 13(6): 932-951.
21.Osman IF, Najafzadeh M, Sharma V, Shukla RK, Jacob B, Dhawan A, Anderson D. TiO2 NPs Induce DNA Damage in Lymphocytes from Healthy Individuals and Patients with Respiratory Diseases-An Ex Vivo/In Vitro Study. J Nanosci Nanotechnol. 2018; 18(1): 544-555.
22.Uboldi C, Urbán P, Gilliland D, Bajak E, Valsami-Jones E, Ponti J, Rossi F. Role of the crystalline form of titanium dioxide nanoparticles: Rutile, and not anatase, induces toxic effects in Balb/3T3 mouse fibroblasts. Toxicol In Vitro. 2016; 31: 137-145.
23.do Carmo T, Azevedo V, de Siqueira P, Galvão T, Dos Santos F, Dos Reis Martinez C, Appoloni CR, Fernandes MN. Reactive oxygen species and other biochemical and morphological biomarkers in the gills and kidneys of the Neotropical freshwater fish, Prochilodus lineatus, exposed to titanium dioxide (TiO2) nanoparticles. Environ Sci Pollut Res Int. 2018; 25(23): 22963-22976.
24.Valdiglesias V, Costa C, Sharma V, Kiliç G, Pásaro E, Teixeira JP, Dhawan A, Laffon B. Comparative study on effects of two different types of titanium dioxide nanoparticles on human neuronal cells. Food Chem Toxicol. 2013; 57: 352-361.
25.Pandurangan M, Enkhtaivan G, Young JA, Hoon HJ, Lee H, Lee S, Kim DH. In vitro therapeutic potential of TiO2 nanoparticles against human cervical carcinoma cells. Biol Trace Elem Res. 2016; 171(2): 293-300.
26.Rahmani NK, Rasmi Y, Abbasi A, Koshoridze N, Shirpoor A, Burjanadze G, Saboory E. Bio-Effects of TiO2 Nanoparticles on Human Colorectal Cancer and Umbilical Vein Endothelial Cell Lines. Asian Pac J Cancer Prev. 2018; 19(10): 2821-2829.
27.Kheirollahi A, Pordeli M, Safavi M, Mashkouri S, Naimi-Jamal MR, Ardestani SK. Cytotoxic and apoptotic effects of synthetic benzochromene derivatives on human cancer cell lines. Naunyn Schmiedebergs Arch Pharmacol. 2014; 387(12): 1199-1208.
28.Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007; 35(4): 495-516.
29.Debnath A, McKerrow JH. Drug Development for Parasite-induced Diarrheal Diseases. Front Microbiol. 2017; 8: 1-3.
30.Holliday DL, Speirs V. Choosing the right cell line for breast cancer research. Breast Cancer Res. 2011; 13(4): 1-7.
31.Dias K, Dvorkin-Gheva A, Hallett RM, Wu Y, Hassell J, Pond GR, Levine M, Whelan T, Bane AL. Claudin-low breast cancer; clinical & pathological characteristics. PLoS One. 2017; 12(1): 1-17.
32.Gioia M, Michaletti A, Scimeca M, Marini M, Tarantino U, Zolla L, Coletta M. Simulated microgravity induces a cellular regression of the mature phenotype in human primary osteoblasts. Cell Death Discov. 2018; 4(1): 1-14.
33.Song M, Zhang R, Dai Y, Gao F, Chi H, Lv G, Chen B, Wang X. The in vitro inhibition of multidrug resistance by combined nanoparticulate titanium dioxide and UV irradition. Biomaterials. 2006; 27(23): 4230-4238.
34.Garcia-Contreras R, Kanagawa S, Beppu Y, Nagao T, Sakagami H, Nakajima H, Shimada J, Adachi K. Morphological features of osteoblasts cultured on ultraviolet-irradiated titanium plates. in vivo. 2011; 25(4): 649-655.
35.Vaquer S, Cuyàs E, Rabadán A, González A, Fenollosa F, de la Torre R. Active transmembrane drug transport in microgravity: a validation study using an ABC transporter model. F1000Research. 2014; 3: 1-15.
36.Lu SK, Bai S, Javeri K, Brunner LJ. Altered cytochrome P450 and P-glycoprotein levels in rats during simulated weightlessness. Aviat Space Environ Med. 2002; 73(2): 112-118.
37.Goldermann M, Hanke W. Ion channel are sensitive to gravity changes. Microgravity Sci Technol. 2001; 13(1): 35-38.
38.Nicolis G, Prigogine I. Symmetry breaking and pattern selection in far-from-equilibrium systems. Proc Natl Acad Sci U S A. 1981; 78(2): 659-663.
Nanomedicine Journal
Volume 6, Issue 2
April 2019
Pages 120-127

Files

Share

How to cite

Statistics