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

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.

Activity Changes of the Peptic Lactoferrin Hydrolysate in Human Gastric Cancer AGS Cells in Response to Cu(II) or Mn(II) Addition

“…Several peptides from natural food hydrolysates have aroused some researchers' great interest; among these assessed proteins is lactoferrin (LF) that exists in milk and dairy foods. Previous studies had proposed that both LF and a LF derivative lactoferricin B had in vitro anti-cancer activities against two gastric cancer SGC-7901 and AGS cells [8,10]; their results also proved that both LF and lactoferricin B had pro-apoptosis to the cells. Recently, researchers have also paid special attention to the potential interaction between proteins and other dietary components.…”

“…Moreover, lactoferrin upon being hydrolyzed by pepsin will yield the important product lactoferricin B, which has been proved to cause cell apoptosis in two gastric cancer cells [5,6]. A previous study of our group also indicated that fortified metal (Cu 2+ or Mn 2+ ) lactoferrin hydrolysates were responsible for apoptosis of AGS and BGC cells [7,8].…”

Combined integrin αvβ3 and lactoferrin receptor targeted docetaxel liposomes enhance the brain targeting effect and anti-glioma effect

“…Then Lf-LP-DTX and RGD-Lf-LP-DTX were prepared [ 3 ]. Lf grafting rate was determined by the BCA assay kit [ 16 ].…”

Antitumoral Properties of Natural Products

“…Of particular interest is the in vivo observation that Zey effectively inhibited tumor growth in nude BALB/c mice bearing BGC823 xenografts without any evident cytotoxic effects [18]. Bo et al have investigated the anticancer activity of bovine lactoferrin hydrolysate (BLH) with added Cu 2+ and Mn 2+ on human gastric cancer BGC-823 cells [19]. They showed that the fortified BLH products had higher activities than BLH alone as evidenced by induction of apoptosis and activation of the classic caspase-3-dependent apoptotic pathway [19].…”

“…Bo et al have investigated the anticancer activity of bovine lactoferrin hydrolysate (BLH) with added Cu 2+ and Mn 2+ on human gastric cancer BGC-823 cells [19]. They showed that the fortified BLH products had higher activities than BLH alone as evidenced by induction of apoptosis and activation of the classic caspase-3-dependent apoptotic pathway [19]. As opposed to the use of single purified molecules, several studies have highlighted the anticancer effects of plant-derived fractions and/or extracts on different cell models.…”