Induction of apoptosis and autophagy via regulation of AKT and JNK mitogen-activated protein kinase pathways in breast cancer cell lines exposed to gold nanoparticles loaded with TNF-α and combined with doxorubicin

Author:

Jawad Marwa H.12,Jabir Majid S.3,Ozturk Kamile2,Sulaiman Ghassan M.3,Abomughaid Mosleh M.4,Albukhaty Salim56,Al-kuraishy Hayder M.7,Al-Gareeb Ali I.7,Al-Azzawi Waleed K.8,Najm Mazin A. A.9,Jawad Sabrean F.10

Affiliation:

1. Department of Biology, College of Science, University of Karbala, Karbala , Iraq

2. Division of Molecular Biology, Department of Biology, Faculty of Science and Letter, Aksaray University , 68100 Aksaray , Turkey

3. Division of Biotechnology, Department of Applied Sciences, University of Technology , 10066 Baghdad , Iraq

4. Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha , Bisha 67714 , Saudi Arabia

5. Department of Chemistry, College of Science, University of Misan , Maysan 62001 , Iraq

6. College of Medicine, University of Warith Al-Anbiyaa , Karbala , Iraq

7. Department of Clinical Pharmacology Medicine and Therapeutic, Medical Faculty, College of Medicine, Mustansiriyah University , P.O. BOX 14132 , Baghdad , Iraq

8. Department of Dentistry, Al-Farahidi University , Baghdad , Iraq

9. Department of Pharmaceutical Chemistry, College of Pharmacy, Al-Ayen University , Thi-Qar , Iraq

10. Department of Pharmacy, Al-Mustaqbal University College , 51001 Hillah , Babylon , Iraq

Abstract

Abstract Gold nanoparticles (GNPs) tagged with peptides are pioneers in bioengineered cancer therapy. The aim of the current work was to elucidate the potential anticancer interactions between doxorubicin and GNPs loaded with tumor necrosis factor-alpha (TNF-α). To investigate whether GNPs loaded with TNF and doxorubicin could stimulate autophagy and apoptosis in breast cancer cells. Two human breast cancer cell lines, MCF-7 and AMJ-13, as well as different apoptotic and autophagy markers, were used. In both cell types, treatment with TNF-loaded GNPs in conjunction with doxorubicin increased the production of apoptotic proteins including Bad, caspase-3, caspase-7, and p53 with upregulation of the LC3-II and Beclin1 proteins. In addition, the findings showed that the mitogen-activated protein kinase signaling pathway was dramatically affected by the GNPs loaded with TNF-α and combined with doxorubicin. This had the effect of decreasing p-AKT while simultaneously increasing p-JNK1/2. The findings demonstrated that GNPs loaded with TNF-α and combined with doxorubicin can induce both autophagy and apoptosis in breast cancer cells. These results suggest that TNF- and doxorubicin-loaded GNPs provide a therapeutic option as a nanomedicine to inhibit the proliferation of breast cancer.

Publisher

Walter de Gruyter GmbH

Subject

Surfaces, Coatings and Films,Process Chemistry and Technology,Energy Engineering and Power Technology,Biomaterials,Medicine (miscellaneous),Biotechnology

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