• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.548-555
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• 2008

Rubiae radix belonging to the family Rubiaceae have been used in traditional medicine to blood stasis and hemostasis. In this study, we reported that methanol extract of Rubiae radix (RRME) induced apoptotic cell death through MAPKs activation in human promylocytic leukemia (HL-60) cells. The cytotoxic activity of activity of RRME in HL-60 cells was increased in a dose-dependent manner. RRME was cytotoxic to HL-60 cells, with IC50 of $8{\mu}g/mL$. Treatment of RRME to HL-60 cells showed apoptotic bodies, and the fragmentation of DNA, suggesting that these cells underwent apoptosis. Caspase-3 activity and PARP cleavage were time-dependently increased the expression of Bcl-2 and Bax. And ratio of Bax/Bcl-2 protein expression. Activation of p38 and JNK were increased 6 hr after RRME treatment in HL-60 cells, but activation of ERK was reduced 24 hr after treatment. Taken together, these results suggest that RRME induces apoptotic cell death through activation of p38 and JNK in HL-60 cells.

• BMB Reports
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• v.47 no.8
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• pp.433-438
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• 2014

Plant sterols have shown potent anti-proliferative effects and apoptosis induction against breast and prostate cancers. However, the effect of sterols against hepatic cancer has not been investigated. In the present study, we assessed whether the stigmasterol isolated from Navicula incerta possesses apoptosis inductive effect in hepatocarcimona (HepG2) cells. According to the results, Stigmasterol has up-regulated the expression of pro-apoptotic gene expressions (Bax, p53) while down-regulating the anti-apoptotic genes (Bcl-2). Probably via mitochondrial apoptosis signaling pathway. With the induction of apoptosis caspase-8, 9 were activated. The DNA damage and increase in apoptotic cell numbers were observed through Hoechst staining, annexin V staining and cell cycle analysis. According to these results, we can suggest that the stigmasterol shows potent apoptosis inductive effects and has the potential to be tested as an anti-cancer therapeutic against liver cancer.

• Korean Journal of Veterinary Research
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• v.52 no.4
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• pp.259-262
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• 2012

Classical swine fever (CSF) is a highly contagious disease among swine that has an important economic impact on worldwide. One clinical symptom of CSF is leukopenia, in particular lymphopenia, which is a characteristic event that occurs early in the course of CSF. Though lymphopenia associated with apoptosis, the pathogenic mechanism underlying the lymphopenia has not been well studied. To understand these mechanisms, we investigated the response of porcine B cell lines to infection with SW03, virulent strain isolated from swine tissue in Korea. This study demonstrated that SW03-infected L35 cell were induced apoptosis through the detection of activated caspase-3. In addition, SW03 infection leaded to alterations in pro-apoptotic, Bax, and anti-apoptotic, Bcl-xL proteins of Bcl-2 family. Our results would suggest that SW03-infected L35 cells induced apoptosis via intrinsic mitochondrial pathway.

• Biomedical Science Letters
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• v.17 no.3
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• pp.177-184
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• 2011

Potassium cyanate (KOCN) is an inorganic compound and induces the carbamylation of proteins with cytotoxic effects on human cells. Although there is a potential cytotoxic molecule, the role of KOCN on the apoptosis of cancer cell is not well understood. The present study investigated the effects of KOCN on the human colorectal cancer cell line, HCT 116 cells. To understand the anti-cancer effect of KOCN on HCT 116 cells, we examined alteration of apoptosis, the intracellular $Ca^{2+}$ concentration, the intracellular signaling pathway and generation of reactive oxygen species (ROS) in these cells treated with KOCN. The apoptosis of HCT 116 cells was induced by KOCN in a dose-dependent manner at 24 hours and 48 hours, respectively. The apoptosis was processed via the cleavage of poly ADP-ribose polymerase (PARP) and activation of caspase 3 in HCT 116 cells. KOCN induced the elevation of intracellular $Ca^{2+}$ concentration and changed the expressions of Bcl-2 family proteins. The pro-apoptotic Bax was continuously up-regulated, and the anti-apoptotic Bcl-2 was down-regulated by KOCN. KOCN also induced the hyperpolarization of mitochondria and the generation of ROS in HCT 116 cells. Taken together, these results indicate that KOCN induces the apoptosis of HCT 116 cells by disruption of $Ca^{2+}$ homeostasis and via mitochondrial pathway. This study provides the compound that may be used as a potent agent for the treatment of colorectal cancer.

• YAKHAK HOEJI
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• v.45 no.6
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• pp.730-738
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• 2001

Apoptosis is a morphologically and biochemically distinct form of cell death that occurs in many different cell types in a wide variety of organisms. Ajbizzia julibrissin belonging the family Leguminosae has been used for the treatment of contusion, sore throat, amnesia, and insomnia in oriental traditional medicine. This study investigates whether the water extract off julibrissin induce apoptotic cell death in Jurkat T-acute lymphoblastic leukemia (ALL) cells. Jurkat cells were increased inhibitions of cell viability in a concentration-dependent manner by A julibrissin. This herbal medicine also caused apoptosis as measured by cell morphology and DNA fragmentation. The capability oft julibrissin to induce apoptosis was associated with proteolytic cleavage of specific target protein such as poly (ADP-ribose) polymerase (PARP) protein suggesting the possible involvement of caspases. Our result skewed that Bcl-2 and Bax protein levels were not changed in all A julibrissin-treated groups compared to control group. These results suggest that A julibrissin-mediated apoptosis is independent with Bcl-2 related signaling pathway in this cells.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.41-47
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• 2019

The apoptotic effects of shikonin (5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione) on the human colon cancer cell line SNU-407 were investigated in this study. Shikonin showed dose-dependent cytotoxic activity against SNU-407 cells, with an estimated $IC_{50}$ value of $3{\mu}M$ after 48 h of treatment. Shikonin induced apoptosis, as evidenced by apoptotic body formation, sub-G_1$ phase cells, and DNA fragmentation. Shikonin induced apoptotic cell death by activating mitogen-activated protein kinase family members, and the apoptotic process was mediated by the activation of endoplasmic reticulum (ER) stress, leading to activation of the $PERK/elF2{\alpha}/CHOP$ apoptotic pathway, and mitochondrial $Ca^{2+}$ accumulation. Shikonin increased mitochondrial membrane depolarization and altered the levels of apoptosis-related proteins, with a decrease in B cell lymphoma (Bcl)-2 and an increase in Bcl-2-associated X protein, and subsequently, increased expression of cleaved forms of caspase-9 and -3. Taken together, we suggest that these mechanisms, including MAPK signaling and the ER- and mitochondria-mediated pathways, may underlie shikonin-induced apoptosis related to its anticancer effect.

• Journal of Life Science
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• v.26 no.5
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• pp.555-562
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• 2016

In this study, we investigated the effects of Undaria pinnatifida (UP), Petalonia binghamiae (PB) and Punctaria latifolia (PL) extracts on the inhibition of proliferation and apoptosis in human gastric and breast cancer cells. AGS, MDA-MB-231 and SK-BR-3 cells were treated with 0, 50, 100, and 200 μg/ml concentrations of the extracts to determine their anti-proliferative effects, using the MTT assay. The UP, PB and PL extracts inhibited proliferation of AGS, MDA-MB-231 and SK-BR-3 cells in a dose-dependent manner, and the PL extract was found to be the most effective. DAPI staining was also performed to determine changes in the cell nucleus. Further, the AGS, MDA-MB-231 and SK-BR-3 cells were treated with 0, 50, 100, and 200 μg/ml of only the PL extract. DAPI staining showed increased chromatin condensation, which is indicative of apoptosis, in the 200 μg/ml group. The expression of the Bax, Bcl-2, and PARP proteins in AGS, MDA-MB-231 and SK-BR-3 cells treated with the PL extract was also determined by western blot analysis. The expression of Bax (a pro-apoptotic protein) and cleaved-PARP was increased, whereas the expression of Bcl-2 (an anti-apoptotic protein) was decreased compared with the control. These findings indicate that the PL extract may have potential as an alternative anticancer drug and nutraceutical.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.25-32
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• 2014

Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory responses. NO is produced by nitric oxide synthase (NOS), and NOS is abundantly expressed in the human dental pulp cells (HDPCs). NO produced by NOS can be cytotoxic at higher concentrations to HDPCs. However, the mechanism by which this cytotoxic pathway is activated in cells exposed to NO is not known. The purpose of this study was to elucidate the NO-induced cytotoxic mechanism in HDPCs. Sodium nitroprusside (SNP), a NO donor, reduced the viability of HDPCs in a dose- and time-dependent manner. We investigated the in vitro effects of nitric oxide on apoptosis of cultured HDPCs. Cells showed typical apoptotic morphology after exposure to SNP. Besides, the number of Annexin V positive cells was increased among the SNP-treated HDPCs. SNP enhanced the production of reactive oxygen species (ROS), and N-acetylcysteine (NAC) ameliorated the decrement of cell viability induced by SNP. However, a soluble guanylate cyclase inhibitor (ODQ) did not inhibited the decrement of cell viability induced by SNP. SNP increased cytochrome c release from the mitochondria to the cytosol and the ratio of Bax/Bcl-2 expression levels. Moreover, SNP-treated HDPCs elevated activities of caspase-3 and caspase-9. While pretreatment with inhibitors of caspase (z-VAD-fmk, z-DEVD-fmk) reversed the NO-induced apoptosis of HDPCs. From these results, it can be suggested that NO induces apoptosis of HDPCs through the mitochondria-dependent pathway mediated by ROS and Bcl-2 family, but not by the cyclic GMP pathway.

• International Journal of Oral Biology
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• v.32 no.2
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• pp.51-57
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• 2007

Cyclosporin A (CsA) plays an important role in clinical medicine and basic biology as an immunosuppressant and a mitochondrial permeability blocker, respectively. It was reported that CsA has a protective role by preventing apoptosis and promoting the proliferation in severed neurons. However, the molecular mechanisms for CsA-induced neuronal cell proliferation are unclear. In this study, we examined the mechanisms underlying the CsA-induced proliferation of PC12 cells. CsA increased the viability of PC12 cells in a dose(over $0.1{\sim}10\;{\mu}M$)-and time-dependent manner. The level of ROS generation was decreased in the CsA-treated PC12 cells. Expression of Bcl-2, an antiapoptotic molecule that inhibits the release of cytochrome c from the mitochondria into the cytosol, was upregulated, whereas Bax, a proapototic molecule, was not changed in the CsA-treated PC12 cells. CsA downregulated the mRNA expression of VDAC 1 and VDAC 3, but VDAC 2 was not changed in the CsA-treated PC12 cells. The level of cytosolic cytochrome c released from the mitochondria and the caspase-3 activity were attenuated in the CsA-treated PC12 cells. These results suggest that the mitochondria-mediated apoptotic signal and Bcl-2 family may play an important role in CsA-induced proliferation in PC12 cells.