Graphene oxide and its nanocomposites with EDTA or chitosan induce apoptosis in MCF-7 human breast cancer.

Ahmed S Doghish,Al-Aliaa M Sallam,Waleed F Khalil,Gharieb S El-Sayyad,Waleed M A El Rouby

doi:10.1039/d1ra04345e

Abstract

To achieve the advanced anticancer activity of nanocomposites fabricated with graphene oxide (GO), a novel procedure was used during the fabrication of chitosan (CS) or ethylene diamine tetra acetic acid (EDTA). The synthesized GO-based nanocomposites were distinguished through different analytical techniques. The cytotoxic activity was examined using MTT assays against three different cancer cell lines. Cell cycle distribution and apoptosis were studied by flow cytometry. Caspase-8, caspase-9, and VEGFR-2 levels were determined using the ELISA technique. HRTEM results revealed a regular 2D thin sheet with a transparent surface in non-modified GO and for GO-CS, the surface of GO has clear cuts and lines had developed due to CS insertion. Concerning the MCF-7 breast cancer cell line, the lowest IC50 values were recorded, suggesting the most powerful cytotoxic effect on breast cancer cells. Treatment with GO-EDTA resulted in the lowest IC50 value of 3.8 ± 0.18 μg mL−1. As indicated by the annexin V-FITC apoptosis assay, the total apoptosis highest percentage was in GO-EDTA treatment (30.12%). In addition, the study of cell cycle analysis showed that GO-EDTA arrested the cell cycle primarily in the G0/G1 phase (33.74%). CS- and EDTA-conjugated GO showed an anti-cancer activity through their cytotoxic effect against the MCF-7 breast cancer cell line.

Highlights

Cancer is considered the second leading cause of death in the world.[1]
It was found that graphene oxide (GO)-ethylene diamine tetra acetic acid (EDTA) is an engaging adsorbent utilized for heavy metal and dangerous bacteria elimination
Dulbecco's modi ed Eagle's medium (DMEM), fetal bovine serum (FBS), phosphate buffer saline (PBS), penicillin/streptomycin (Pen/Strep) solution (Pen/Strep), and trypsin-EDTA were purchased from Gibco (Gibco, TFS, Inc., USA)

Summary

Introduction

The application of nanotechnology in cancer is an evolving eld of research involving cooperation between different disciplines, including biology, chemistry, engineering, and medicine. EDTA is a cost-efficient chemical, usually-used as a chelating factor and applied in different purposes such as industrial laundry, in medical analysis as an anticoagulant agent, and for atomic power as a detergent.[32] The antimicrobial and antitumor strength of EDTA due to the chelating means which develops through the cooperation with metal systems in microbial and cancer cells, which makes it an efficient center for microbial and cancer treatment.[2,33] The design of the EDTA functional groups inside the outer surface of GO can basically advance the adsorption capacity and biomedical potential of GO sheets.[25,34,35] It was found that GO-EDTA is an engaging adsorbent utilized for heavy metal and dangerous bacteria elimination. Possible anticancer activity determinations by cell viability assay, ow cytometric study for cell cycle and apoptosis exposure, and evaluation of caspase-8 and caspase-9 activities and VEGFR-2 were performed

Materials and methods

Results and discussion

Conclusions