The Synergistic Anticancer Traits of Graphene Oxide Plus Doxorubicin Against BT474 and MCF7 Breast Cancer Stem Cells In Vitro.

Mahsa Ebrahimi,Maryam Teimouri,Mehdi Pooladi

doi:10.1007/s12010-021-03623-8

Abstract

Breast cancer is among the leading causes of death due to cancers around the globe. Current therapeutic approaches towards healing of breast cancer have been associated with poor outcomes. Graphene and its derivatives have a two-dimensional flat structure, which is characterized by the ability to carry drugs and modify the surface, low cytotoxicity, and high biocompatibility. This study was performed on MCF7 and BT474 human breast cancer cells. Different concentrations of doxorubicin (DOX), graphene oxide (GO), and graphene oxide plus doxorubicin (GO-DOX) were subjected to both cell lines at specified intervals. At the end of the treatments, MTT test was applied to determine the viability of cells, and then flow cytometry, colony formation, and spheroid tests were implemented in both cell lines treated with DOX, GO, and GO-DOX components. We used DLS and TEM to confirm the GO properties. According to the MTT test results, 1 μL of DOX at 10mg/ml (equivalent to 0.1mg/ml) caused 50% survival of MCF7 cells at 24h. In both cell lines, an increase in apoptosis occurred after incubation with GO and DOX. Although a rate of mortality of MCF-7 cells was due to necrosis, the BT474 cell death was merely through the apoptosis. Furthermore, the results of the colony formation test outlined an enhancing inhibitory effect in the presence of GO-DOX as a comparison to the control. Additionally, spheroids formed following treatment with GO-DOX exhibited a significant decrease compared to their control group, with an increase in the number of spheroids in BT474 cells compared to those in the MCF-7. The decreasing effect of compounds against the migration and cell invasion potential was also observed, being higher in MCF7 than BT474 cells. The effects of cytotoxic GO were observed at higher concentrations.

Highlights

Cancer is a group of diseases due to the uncontrolled division of cells in the body
Flow cytometry was used to evaluate the extent of apoptosis in MCF7 and BT474 cancer cell lines as a result of incubation with graphene oxide (GO) and DOX (GO-DOX) compared to the control and DOX groups
The results revealed that in both cell lines an increase in the apoptosis was occurred following incubation with GO plus DOX (GO-DOX), with an alternative induction of necrosis in MCF-7 cells

Summary

Introduction

Cancer is a group of diseases due to the uncontrolled division of cells in the body. Cancer is a substantial increasing worldwide problem occurred in numerous forms causing the death of more than a third of the world's population. The disease is growing rapidly in developed countries because of alterations in population and risk factors resulted from negative impact of environmental factors increased in a variety of cancers [1,2,3]. Breast cancer is the predominant cancer among various age groups of women, accounting for 25% of all cancers, there is currently no definitive and permanent treatment for this complex disease, though has occurred for a long time. High death rate and lasting time of diagnosis, high costs and side effects of chemotherapy are additional concerns. Seeking effective therapeutic approaches is promising in promoting the health of the global community [4,5]

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