Nano Milk Protein-Mucilage Complexes: Characterization and Anticancer Effect

El-Maksoud, Ahmed A. Abd; Makhlouf, Amal; Altemimi, Ammar B.; El-Ghany, Ismail H. Abd; Nassrallah, Amr; Cacciola, Francesco; Abedelmaksoud, Tarek Gamal

doi:10.3390/molecules26216372

Cited by 5 publications

(1 citation statement)

References 53 publications

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“…To eliminate this possibility, a viable idea is to decipher the active region in SEM-Mb responsible for anti-leukemia activity and then use this active region to develop peptidomimetics. Notably, El-Maksound et al [65] reported that milk protein-mucilage complexes formed by milk proteins with Isabgol husk mucilage or Ziziplus spina-christi mucilage enhanced the anti-cancer activity of milk proteins. As reducing the dose and frequency of using SEM-Mb can delay its potential antibody induction, complexation of SEM-Mb with natural components may be a feasible strategy to increase its anti-leukemia activity at a reduced dose.…”

Section: Discussionmentioning

confidence: 99%

Carboxyl Group-Modified Myoglobin Induces TNF-α-Mediated Apoptosis in Leukemia Cells

et al. 2022

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Previous studies have shown that chemical modification may increase the activity of proteins or confer novel activity to proteins. Some studies have indicated that myoglobin (Mb) is cytotoxic; however, the underlying mechanisms remain unclear. In this study, we investigated whether chemical modification of the carboxyl group by semicarbazide could promote the Mb cytotoxicity in human leukemia U937 cells and the underlying mechanism of semicarbazide-modified myoglobin (SEM-Mb)-induced U937 cell death. The semicarbazide-modified Mb (SEM-Mb) induced U937 cell apoptosis via the production of cleaved caspase-8 and t-Bid, while silencing of FADD abolished this effect. These findings suggest that SEM-Mb can induce U937 cell death by activating the death receptor-mediated pathway. The SEM-Mb inhibited miR-99a expression, leading to increased NOX4 mRNA and protein expression, which promoted SIRT3 degradation, and, in turn, induced ROS-mediated p38 MAPK phosphorylation. Activated p38 MAPK stimulated miR-29a-dependent tristetraprolin (TTP) mRNA decay. Downregulation of TTP slowed TNF-α mRNA turnover, thereby increasing TNF-α protein expression. The SEM-Mb-induced decrease in cell viability and TNF-α upregulation were alleviated by abrogating the NOX4/SIRT3/ROS/p38 MAPK axis or ectopic expression of TTP. Taken together, our results demonstrated that the NOX4/SIRT3/p38 MAPK/TTP axis induces TNF-α-mediated apoptosis in U937 cells following SEM-Mb treatment. A pathway regulating p38 MAPK-mediated TNF-α expression also explains the cytotoxicity of SEM-Mb in the human leukemia cell lines HL-60, THP-1, K562, Jurkat, and ABT-199-resistant U937. Furthermore, these findings suggest that the carboxyl group-modified Mb is a potential structural template for the generation of tumoricidal proteins.

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Section: Discussionmentioning

confidence: 99%