γ-Tocotrienol, a kind of isoprenoid phytochemical, has antitumor activity. However, there is limited evidence that it has an effect on cervical cancer. In this study, the capacity to inhibit proliferation and induce apoptosis in human cervical cancer HeLa cells and the mechanism underlying these effects were examined. The results indicated that a γ-tocotrienol concentration over 30 μM inhibited the growth of HeLa cells with a 50% inhibitory concentration (IC50) of 46.90 ± 3.50 μM at 24 h, and significantly down-regulated the expression of proliferative cell nuclear antigen (PCNA) and Ki-67. DNA flow cytometric analysis indicated that γ-tocotrienol arrested the cell cycle at G0/G1 phase and reduced the S phase in HeLa cells. γ-tocotrienol induced apoptosis of HeLa cells in a time- and dose-dependent manner. γ-tocotrienol-induced apoptosis in HeLa cells was accompanied by down-regulation of Bcl-2, up-regulation of Bax, release of cytochrome from mitochondria, activation of caspase-9 and caspase-3, and subsequent poly (ADP-ribose) polymerase (PARP) cleavage. These results suggested that γ-tocotrienol could significantly inhibit cell proliferation through G0/G1 cell cycle arrest, and induce apoptosis via the mitochondrial apoptotic pathway in human cervical cancer HeLa cells. Thus, our findings revealed that γ-tocotrienol may be considered as a potential agent for cervical cancer therapy.
The effects of in vitro batch digestion on water-in-oil-in-water (W/O/W) double emulsions encapsulated with anthocyanins (ACNs) from grape skin were investigated. The double emulsions exhibited the monomodal distribution (d = 686 ± 25 nm) showing relatively high encapsulation efficiency (87.74 ± 3.12%). After in vitro mouth digestion, the droplet size (d = 771 ± 26 nm) was significantly increased (p < 0.05). The double W1/O/W2 emulsions became a single W1/O emulsion due to proteolysis, which were coalesced together to form big particles with significant increases (p < 0.01) of average droplet sizes (d > 5 µm) after gastric digestion. During intestinal digestion, W1/O droplets were broken to give empty oil droplets and released ACNs in inner water phase, and the average droplet sizes (d < 260 nm) decreased significantly (p < 0.05). Our results indicated that ACNs were effectively protected by W/O/W double emulsions against in vitro mouth digestion and gastric, and were delivered in the simulated small intestine phase.
1 December 2020 in International Journal of Biological Macromolecules
Bovine milk fat globule membrane (MFGM) has shown many health benefits, however, there has not been much study on non-cattle MFGMs. The purpose of this study was to compare the anti-proliferation effects and investigate the mechanisms of MFGMs from bovine, goat, buffalo, yak and camel milk in HT-29 cells. Results showed that protein content in MFGM of yak milk is the highest among five MFGM. All MFGMs reduced cellular viability which was in agreement with cell morphology and apoptosis. However, the number of cells in S-phase from 24 h to 72 h was increased significantly by treatment with goat, buffalo and bovine MFGMs (100 μg/mL), but not yak and camel. All MFGMs treatment significantly reduced the mitochondrial membrane potential (with an order of goat > buffalo > bovine > camel > yak) and Bcl-2 expression, but increased the expression of both Bax and Caspase-3. Taken together, the results indicate that all MFGMs, especially goat and buffalo MFGMs, showed better effects at inducing apoptosis and reduction the viability of HT-29 cells. The mechanism might be arresting the cell cycle at S phase, depolarization of mitochondrial membrane potential, down-regulation of Bcl-2 expression and increase of Bax and Caspase-3 expression.
The mechanism of γ-T3-induced proliferation and differentiation of MC3T3-E1 cells via the activation of the Wnt/β-catenin signaling pathway by allowing the stabilization and nuclear translocation of β-catenin.
Gamma-tocotrienol, a major component of tocotrienol-rich fraction of palm oil, has been suggested to exhibit bone protective effectsin vivo. However, the effects ofγ-tocotrienol on osteoblast cells are still unclear. In this study, the effects ofγ-tocotrienol on the proliferation, differentiation, and mineralization in osteoblastic MC3T3-E1 cells were investigated. Our results showed thatγ-tocotrienol (2–8 μmol/L) significantly improved the cell proliferation (), but it did not affect cell cycle progression.γ-Tocotrienol significantly increased alkaline phosphatase (ALP) activity (), secretion levels of osteocalcin (OC) and osteonectin (ON), and mRNA levels of collagen type I (Col I) of MC3T3-E1 cells. Meanwhile, we found thatγ-tocotrienol is promoted in differentiation MC3T3-E1 cells by upregulation of the expression of Runx2 protein. Moreover, the number of bone nodules increased over 2.5-fold in cells treated withγ-tocotrienol (2–8 μmol/L) for 24 d compared to control group. These results indicated thatγ-tocotrienol at low dose levels, especially 4 μmol/L, could markedly enhance the osteoblastic function by increasing the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. Moreover, our data also indicated that Runx2 protein may be involved in these effects. Further studies are needed to determine the potential ofγ-tocotrienol as an antiosteoporotic agent.