Effect of Cu/Mn-Fortification on In Vitro Activities of the Peptic Hydrolysate of Bovine Lactoferrin against Human Gastric Cancer BGC-823 Cells.

Li-Ying Bo,Tie-Jing Li,Xin-Huai Zhao

doi:10.3390/molecules24071195

Li-Ying Bo, Tie-Jing Li + Show 1 more

Open Access

https://doi.org/10.3390/molecules24071195

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Abstract

Bovine lactoferrin hydrolysate (BLH) was prepared with pepsin, fortified with Cu2+ (Mn2+) 0.64 and 1.28 (0.28 and 0.56) mg/g protein, and then assessed for their activity against human gastric cancer BGC-823 cells. BLH and the four fortified BLH products dose- and time-dependently had growth inhibition on the cells in both short- and long-time experiments. These samples at dose level of 25 mg/mL could stop cell-cycle progression at the G0/G1-phase, damage mitochondrial membrane, and induce cell apoptosis. In total, the fortified BLH products had higher activities in the cells than BLH alone. Moreover, higher Cu/Mn fortification level brought higher effects, and Mn was more effective than Cu to increase these effects. In the treated cells, the apoptosis-related proteins such as Bad, Bax, p53, cytochrome c, caspase-3, and caspase-9 were up-regulated, while Bcl-2 was down-regulated. Caspase-3 activation was also evidenced using a caspase-3 inhibitor, z-VAD-fmk. Thus, Cu- and especially Mn-fortification of BLH brought health benefits such as increased anti-cancer activity in the BGC-823 cells via activating the apoptosis-related proteins to induce cell apoptosis.

Highlights

Dietary proteins provide both essential amino acids and energy for the body, and have several health benefits by the release of so-called bioactive peptides [1], because these peptides have various physiological functions such as anti-cancer, anti-hypertensive, anti-oxidant, mineral-binding, and other effects [2,3]
For LF, Cu supplementation increases immuno-modulation in both murine splenocytes and RAW264.7 macrophages, while Fe addition can enhance growth inhibition and apoptosis induction in the HepG2 cells infected with HBV [11,12]
Bovine lactoferrin hydrolysate (BLH) was measured with a DH value of 5.1 ± 0.1%

Summary

Introduction

Dietary proteins provide both essential amino acids and energy for the body, and have several health benefits by the release of so-called bioactive peptides [1], because these peptides have various physiological functions such as anti-cancer, anti-hypertensive, anti-oxidant, mineral-binding, and other effects [2,3]. The solid fraction from yogurt exerts growth inhibition on initial tumor cells, while the peptide fraction from algae protein has anti-cancer activity against the gastric cancer AGS cells through arresting the cells in the post-G1-phase [4,5]. An important Fe-binding protein lactoferrin (LF) and its derivatives have been assessed for their bio-activities. LF and a LF derivative lactoferricin B have anti-cancer activities in the gastric cancer SGC-7901, AGS cells and oral squamous cell carcinoma [6,7,8]. From a chemical point of view, proteins have various functional groups such as −OH, −SH, −NH, etc., and can interact with some macro-elements and trace elements, resulting in changed nutritive values and bio-activities. For LF, Cu supplementation increases immuno-modulation in both murine splenocytes and RAW264.7 macrophages, while Fe addition can enhance growth inhibition and apoptosis induction in the HepG2 cells infected with HBV [11,12]

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