Effective Targeting of Raf-1 and Its Associated Autophagy by Novel Extracted Peptide for Treating Breast Cancer Cells

Effective Targeting of Raf-1 and Its Associated Autophagy by Novel Extracted Peptide for Treating Breast Cancer Cells

Breast cancer is one of the most common causes of death in women worldwide and has harmful influence on their psychological state during therapy. Multikinase inhibitors have become effective drugs for treating a variety of cancer diseases such as breast cancer. A purified short peptide (H-P) was iso...

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Published in:Frontiers in oncology Vol. 11; p. 682596
Main Authors: El-Fadl, Hebatullah M Abou, Hagag, Naglaa M, El-Shafei, Reham A, Khayri, Mohamed H, El-Gedawy, Gamalat, Maksoud, Ahmed I Abd El, Mohamed, Doaa D, Mohamed, Dalia D, El Halfawy, Ibrahim, Khoder, Ahmed I, Elawdan, Khaled A, Elshal, Mohamed F, Salah, Ahmed, Khalil, Hany
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 27-08-2021
Subjects:
autophagy
breast cancer
honey peptide
Oncology
Raf-1 activation
Sorafenib
breast cancer
autophagy
honey peptide
Sorafenib
Raf-1 activation
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Summary:Breast cancer is one of the most common causes of death in women worldwide and has harmful influence on their psychological state during therapy. Multikinase inhibitors have become effective drugs for treating a variety of cancer diseases such as breast cancer. A purified short peptide (H-P) was isolated from the natural honey and tested for its potential regulatory role in breast cancer cells compared with the effectiveness of the anticancer drug, Sorafenib (SOR), using MCF-7, EFM-19, and MCF-10A cell lines. Furthermore, we investigated the direct connection between Raf-1 activation and cellular autophagy as potential targets of SOR and H-P extract using RNA interference. Interestingly, the treatment with H-P showed competitive regulation of phosphorylated Raf-1, MEK1/2, and matched autophagy-related LC3B without any detectable toxic effects in the non-tumorigenic epithelial cells. Unlike SOR, the regulation of Raf-1 protein and autophagic machinery by the novel H-P extract showed neglected levels of the released proinflammatory cytokine. This regulation of cytokine secretion by H-P resulted in decreasing the expression level of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) in treated cells. Moreover, the transfection of MCF-7 cells with small interference RNA (siRNA) antagonist Raf-1 expression markedly reduced the expression of LC3B, while it increased the expression of NF-kB1 and NF-kB2, indicating the potential cross-link between Raf-1, autophagy, and NF-kB effector. Collectively, these findings suggest that H-P-mediated Raf-1, MEK1/2, LC3B, and NF-kB provide a novel and efficacious multikinase inhibitor for treating breast cancer without detectable cytotoxic effects.
Bibliography:Reviewed by: Ali Bettaieb, Université de Sciences Lettres de Paris, France; Anna Margaretha Joubert, University of Pretoria, South Africa
Edited by: Rizwan Romee, Dana–Farber Cancer Institute, United States
This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Oncology
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2021.682596