Abstract

The anticancer activity of natural compounds has recently attracted multidisciplinary research. In this study, the complexation of milk proteins (MP) with Isabgol husk mucilage (IHM) and Ziziphus spina-christi mucilage (NabM) was investigated. In this context, the physicochemical properties of milk protein mucilage complexes (MPMC) including pH, Carr’s index, water solubility, and water absorption indices were measured, and the flow behavior was studied. In addition, the amino acid profile, protein digestibility, and phenolic and flavonoids content of MPMC were explored, and the microstructure of the complexes was visualized using transmission electron microscopy. The antioxidant and anticancer potencies of MPMC against two cancerous cell lines, human liver cancer HEPG-2 and breast cancer MCF-7, in comparison with two normal cell lines, namely, Bj-1 and MCF-12F, were tested using neutral red uptake assay. The results revealed that MPMC had scavenging activity against DPPH, ABTS, and HS radicals. Moreover, MPMC has the potential to prevent DNA damage induced by oxidative stress in Type-Fenton’s reaction. The results of the neutral red assay showed significant growth inhibition of both HEPG-2, MCF-7, whereas no significant cytotoxic effect was detected against Bj-1 and MCF-12F. RT-qPCR results indicated MPMC stimulated apoptosis as revealed by the upregulation of the pro-apoptosis gene markers Casepase-3, p53, Bax. Meanwhile, the anti-apoptosis Bcl-2 gene was downregulated. However, no significant difference was observed in normal cell lines treated with MPMC. In conclusion, MPMC can be considered as a promising anticancer entity that can be used in the development of novel cancer therapeutics with comparable activity and minimal side effects compared to conventional cancer chemotherapies.

Highlights

  • Cancer is the primary cause of mortality around the world with approximately 10 million deaths in 2020 [1]

  • Such observations are in line with those of Vukic et al who reported the complex formation between whey milk proteins and pectin through electrostatic and hydrophobic interactions which resulted in good consistency of the complex [17]

  • Our results indicated that milk proteins (MP)/Nabeq mucilage (NabM) had higher anticancer activity against HepG-2 and MCF-7 cancer cell lines, with IC50 value 5.13 and 10.07 μg/mL, respectively

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Summary

Introduction

Cancer is the primary cause of mortality around the world with approximately 10 million deaths in 2020 [1]. Diagnosis and the development of novel therapeutics is the only hope to defeat cancer. Conventional cancer treatments such as chemotherapy and radiation are relatively expensive and accompanied by significant side effects. Scientific and research interest is tending to the utilization of natural compounds (i.e., proteins, polysaccharides, and polyphenols) from their sources that have anticarcinogenic potential as they are considered to have less toxic side effects compared to conventional treatments. Polysaccharides from plant sources have recently received increasing attention due to their bioactive properties [2,3]. Numerous studies have been interested in isolating bioactive polysaccharides and polyphenols from natural plant sources such as fruits, vegetables, cereals, and herbs due to their beneficial pharmacological effects [4]

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