Potential anti-tumor activity of 13.56\xa0MHz alternating magnetic hyperthermia and chemotherapy on the induction of apoptosis in human colon cancer cell lines HT29 and HCT116 by up-regulation of Bax, cleaved caspase 3&9, and cleaved PARP proteins

Saba Jahangiri,Vahid Pirhajati Mahabadi,Sakine Shirvalilou,Samideh Khoei,Majid Safa,Sepideh Khoee

doi:10.1186/s12645-021-00108-5

Saba Jahangiri, Vahid Pirhajati Mahabadi + Show 4 more

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https://doi.org/10.1186/s12645-021-00108-5

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Abstract

BackgroundThe purpose of the present study was to evaluate the efficacy of chemo-magnetic hyperthermia (MH), a combination of alternating magnetic field (AMF) and superparamagnetic nanoparticles (SPIONs) coated with Polyethylene glycol-Poly(butyl acrylate)-Polyethylene glycol (PEG-PBA-PEG) carrying 5-Fluorouracil (5-Fu), at inducing apoptosis in the human cancer cell lines HT29 and HCT116. This process can be mediated by alterations in the expression of apoptotic effector proteins, including Bax, Bcl-2, cleaved caspase 3&9, and cleaved PARP, which are involved in the intrinsic pathway of apoptosis. For this purpose, the cells were cultured as monolayers. Then both cell lines were treated with 5-Fu/magnetic nanoparticles and magnetic hyperthermia. Finally, the effect of treatment on cancer cells was determined by Western blot analysis and flow cytometry.ResultsOur results showed that combined chemo-magnetic thermotherapy significantly increased the apoptosis in colon cancer cells compared to chemotherapy or hyperthermia alone (P < 0.05). Up-regulation of Bax, cleaved caspase 3&9, and cleaved PARP proteins was indicative of apoptosis induction in cancer cells, which are involved in the intrinsic pathway of apoptosis.ConclusionsThis study demonstrates that localized hyperthermia was able to significantly trigger the 5-Fu release and inhibit cell viability, which, due to the synchronization of hyperthermia and chemotherapy, exacerbated the damage of cancer cells.Graphical

Highlights

The purpose of the present study was to evaluate the efficacy of chemo-magnetic hyperthermia (MH), a combination of alternating magnetic field (AMF) and superparamagnetic nanoparticles (SPIONs) coated with Polyethylene glycolPoly(butyl acrylate)-Polyethylene glycol (PEG-PBA-PEG) carrying 5-Fluorouracil (5-Fu), at inducing apoptosis in the human cancer cell lines HT29 and HCT116
Colon cancer cell lines The human colon cancer cell lines HT29 and HCT116 were cultured as a monolayer in tissue culture flasks
Temperature had no effect on release rate. 5-Fu was released to the extent of 62.1% and 63.21% from PEG-PBA-PEG superparamagnetic nanoparticles (MNPs)@5-Fu nanoparticles, within approximately 72 h in a PBS at 37 °C and 43 °C, respectively

Summary

Introduction

The purpose of the present study was to evaluate the efficacy of chemo-magnetic hyperthermia (MH), a combination of alternating magnetic field (AMF) and superparamagnetic nanoparticles (SPIONs) coated with Polyethylene glycolPoly(butyl acrylate)-Polyethylene glycol (PEG-PBA-PEG) carrying 5-Fluorouracil (5-Fu), at inducing apoptosis in the human cancer cell lines HT29 and HCT116. This process can be mediated by alterations in the expression of apoptotic effector proteins, including Bax, Bcl-2, cleaved caspase 3&9, and cleaved PARP, which are involved in the intrinsic pathway of apoptosis. We studied two 5-Fu chemoresistance colon cancer cell lines, HT29 and HCT116 (He et al 2017; Huang et al 2019), the former of which is necrosis factor-related apoptosis-inducing ligand (TRAIL) resistant, while the latter is TRAIL sensitive (Lee et al 2011)

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