• Journal of Yeungnam Medical Science
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• v.34 no.2
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• pp.174-181
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• 2017

Ferroptosis is a newly recognized type of cell death that results from iron-dependent lipid peroxidation and is different from other types of cell death, such as apoptosis, necrosis, and autophagic cell death. This type of cell death is characterized by mitochondrial shrinkage with an increased mitochondrial membrane density and outer mitochondrial membrane rupture. Ferroptosis can be induced by a loss of activity of system $X_c{^-}$ and the inhibition of glutathione peroxidase 4, followed by the accumulation of lipid reactive oxygen species (ROS). In addition, inactivation of the mevalonate and transsulfuration pathways is involved in the induction of ferroptosis. Moreover, nicotinamide adenine dinucleotide phosphate oxidase and p53 promote ferroptosis by increasing ROS production, while heat shock protein beta-1 and nuclear factor erythroid 2-related factor 2 inhibit ferroptosis by reducing iron uptake. This article outlines the molecular mechanisms and signaling pathways of ferroptosis regulation, and explains the roles of ferroptosis in human disease.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.363-368
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• 2006

EGCG [(-)-epigallocatechin-3-gallate], a major component of green tea has been considered as a major antioxidant constituent. In addition to having been considered for cancer treatment as a chemopreventive and chemotherapeutic agent, EGCG has recently been attributed an anti-proliferative effect. We re-examined the latter finding in this study and added specific focus on the ability of EGCG to induce apoptosis in human osteogenic sarcoma (HOS) cells. Antiproliferative action of EGCG $(IC_{50}=35.3{\pm}6.0{\mu}g/mL)$ appeared to be linked to apoptotic cell death based on morphological changes, chromosomal DNA degradation, and an increase in the $sub-G_1$ apoptotic cell population. Treatment of HOS cells with EGCG gradually activated caspase-3, an established inducer of apoptotic cell death.

• The Journal of Korean Medicine
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• v.22 no.2
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• pp.64-74
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• 2001

Objectives : The effects of aqueous extract of Backhapgogumtanggami-bang (BGTG, a newly devised herb medicine) on the induction of apoptotic cell death were investigated in human lymphoid origin leukemia cell lines, HL-60. Methods : Cells were treated with various concentrations and $400{\;}\mu\textrm{g}/ml$ BGTG for 12 hr. Genomic DNA was isolated and separated on 1.8% agarose gels. Lysates from the cells were used to measure the activity of caspase-2, -3, -8, and -9 protease by using fluorogenic peptide. Cells were preincubated with SB-203580 for 30 min. Nuclear protein from the cells was incubated with oliginucleotide probe of AP-l and NF-kB. Nuclear extracts from the cells were isolated and reacted with antibodies. Results : The viability of HL-60 cells were markedly decreased by BGTG extract in a dose- and time-dependent manner. BGTG extract induced the apoptotic death of HL-60 cells which was characterized by the DNA fragmentation. The activations of Caspase-2, 3, and 9 were induced by BGTG. However, selective inhibition of the p38 mitogen-activated protein kinase pathways by SB-203580 did not affect the extent of BGTG extract-induced cell death. Furthermore, we observed the transient activations of transcriptional factors such as AP-l and NF-kB. Conclusions : These results suggest that BGTG extract induced apoptotic death of HL-60 cells and caspase activations as well as the modulation of transcriptional factors such as AP-1 and NF-kB.

• Biomedical Science Letters
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• v.7 no.4
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• pp.205-210
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• 2001

Whereas apoptosis is a critical mode of cell deletion in normal organism development, apoptotic cells are also observed in tumor therapy. We therefore investigated the expression of apoptotic cells induced as a function of time and dose in murine A-20 lymphoma treated with cyclophosphamide in vivo, by H&E and TUNEL method. The percent of apoptotic cells were scored from tumor section using TUNEL method. The expression of apoptotic positive cell was determined over a 10-day period following treatment of the mice with 200 mg/kg. Apoptosis increased further with time, reaching a peak value between 12~24 hr (scored 6.7$\pm$1.0%~6.1$\pm$0.7%), and then slowly declined to background levels by 10 days after treatment. The dependence of induction of apoptosis on the dose of cyctophosphamide was determined by treatment with 50, 100, or 200 mg/kg at 12 hr after treatment. Apoptosis was dose dependent in that as the dose was increased the percentage of apoptosis increased. However, the increase in apoptosis at the lower dose used (50 mg/kg) was higher on a per unit dose basis than that at the higher dose used (200 mg/kg). This result show that the alkylating agent cyclophosphamide strongly induces apoptosis in murine lymphoma.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.10
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• pp.1317-1323
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• 2009

In the present study, we investigated the anti-proliferation activity of Citrus grandis Osbeck peel (CGP) in HL60 (human promyelocytic leukemia) cells. It was found that 80% ethanol extract of CGP could inhibit the cell growth in a dose-dependent manner ($250{\sim}1,000{\mu}g/mL$), which was associated with morphological changes and apoptotic cell death such as depolarized mitochondrial membrane, formation of apoptotic bodies and increased populations of apoptotic sub-G1 phase. The results indicate that CGP extract inhibits the growth of HL60 cancer cells by the induction of apoptosis, which may be mediated by its ability to change the Bcl family proteins and increase the activation of caspase-3 and PARP. Therefore, it is suggested that CGP has the potential to provide a remarkable natural defense against the proliferation of HL60 cells.

• Proceedings of the Korean Society of Sericultural Science Conference
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• 2004.10a
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• pp.81-81
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• 2004

• Korean Journal of Veterinary Research
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• v.41 no.2
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• pp.203-210
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• 2001

Here, we compared the effectiveness of 50 MeV($p{\to}RBe^+$) cyclotron fast neutrons versus $^{60}Co$ ${\gamma}$-rays by the apoptotic fragment frequency in both rat peripheral lymphocytes and crypt cells to check a radiobiological endpoint. The incidence of apoptotic cell death was increased in all irradiated groups, and radiation at all doses trigger rapid changes in both crypt cells and peripheral lymphocytes. These data suggest that apoptosis may play an important role in homeostasis of damaged radiosensitive target organ by removing damaged cells. The curve of dose-effect relationship for these data of apoptotic fragments frequencies was $y=0.3+(6.512{\pm}0.279)D(r^2=0.975)$ after neutrons, while $y=0.3+(4.435{\pm}0.473)D+(-1.300{\pm}0.551)D^2(r^2=0.988)$ after ${\gamma}$-rays. In addition, $y=3.5+(118.410{\pm}10.325)D+(-33.548{\pm}12.023)D^2(r^2=0.992)$ after ${\gamma}$-rays in rat lymphocytes. A significant dose-response relationship was found between the frequency of apoptotic cell and dose. These data show a trend towards increase of the numbers of apoptotic cells with increasing dose. Dose-response curves for high and low linear energy transfer (LET) radiation modalities in these studies were different. The relative biological effectiveness (RBE) value for crypt cells was 1.919. In addition, there were significant peaks on apoptosis induction at 4 and 6h after irradiation, and the morphological findings of the irradiated groups were typical apoptotic fragments in crypt cells that were hardly observed in the control group. Thus, apoptosis induction in both crypt cells and peripheral lymphocytes could be a useful endpoint of rat model for studying screening test and microdosimetic indicator to evaluate the biological effects of radiation-induced cell damage.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1226-1232
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• 2007

Phellinus linteus is a well-known Oriental medicinal fungus that has various biological activities, including immunomodulatory and anti-tumor activities, the mechanisms of which are poorly understood. In the present study, we investigated the anti-proliferative activity of the methanol extract of P. linteus-Barley corn (MEPLB) in human lekemic U937 cells. It was found that exposure of U937 cells to MEPLB resulted morphological change and growth inhibition in a dose-dependent manner as measured by trypan blue count and MTT assay. Upon treatment with MEPLB, U937 cells developed many of the hallmark features of apoptosis, including condensation of chromatin and an increase in the sub-G1 population suggesting that the anti-proliferative effect of MEPLB is associated with the induction of apoptosis. The anti-proliferative and apoptotic effects of MEPLB were connected with a marked induction of the pro-apoptotic Bax and cyclin-dependent kinase (Cdk) inhibitor p21 in a p53-independent manner. Additionally, MEPLB treatment significantly induced the caspase-3 activity in U937 cells. Taken together, the present results suggest that apoptotic signals evoked by MEPLB in human leukemic U937 cells may converge caspase-3 activation through an up-regulation of Bax rather than a down-regulation of Bcl-2 or Bel-xL.

• Journal of Life Science
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• v.27 no.11
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• pp.1340-1348
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• 2017

Sanguinarine is a benzophenanthridine alkaloid derived from the roots of Sanguinaria canadensis L., which is used for the purpose of treating various diseases. Although studies of anticancer activities have been performed using various cancer cell lines, the phenomenon of inducing apoptosis in cancer cells by using sanguinarine requires more research. Therefore, this study investigated the anti-cancer activities and related mechanisms of sanguinarine used with Hep3B human hepatocellular carcinoma cells in terms of the regulation of apoptosis. Sanguinarine inhibited the proliferation of Hep3B cells in a concentration-dependent manner, which was associated with the induction of apoptosis. Sanguinarine also increased the activity of caspase-3, which is a typical effector caspase, and the activities of caspase-8 and caspase-9, which are key when initiating extrinsic and intrinsic apoptosis pathways, respectively. In addition, sanguinarine increased the expression of death receptor-related genes and pro-apoptotic BAX, which belongs to the Bcl-2 family, while suppressing the expression of anti-apoptotic Bcl-2. Sanguinarine promoted the truncation of Bid and enhanced the release of cytochrome c from the mitochondria to the cytoplasm due to a loss of mitochondrial membrane potential. Furthermore, the reduction of a survival rate that was induced by sanguinarine and the induction of apoptosis disappeared with the inhibition of artificial caspase activity. Therefore, the results of the study indicated that sanguinarine-induced apoptosis in Hep3B cells involves both extrinsic and intrinsic pathways; such apoptosis is a caspase-dependent phenomenon.

• Journal of Life Science
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• v.23 no.10
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• pp.1252-1259
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• 2013

To investigate the effects of a fibrinolytic enzyme, BK-17, on the growth of human cancer cells, we performed various biochemical experiments, including cell proliferation and viability, and investigated subsequent morphological changes and apoptosis induction. BK-17 treatment of AGS human gastric and T24 human bladder carcinoma cells decreased the viability and the proliferation of the cells in a concentration-dependent manner. Microscopic studies indicated that the antiproliferative effects of the BK-17 treatment were associated with morphological changes, such as membrane shrinking, cell rounding up, and the formation of apoptotic bodies, indicating that BK-17 induced apoptosis in the cell lines. Of note, RT-PCR and Western blotting data indicated that the BK-17 treatment induced the down-regulation of antiapoptotic Bcl-2 members, Bcl-2 and $Bcl-X_L$, and the up-regulation of proapoptotic Bax members, Bax and Bad, in the AGS cells. BK-17-induced apoptosis of AGS cells was involved in the proteolytic activation of caspase-3, caspase-8, and caspase-9. Taken together, these findings suggest that BK-17 is associated with the induction of apoptotic cell death.