• 동의생리병리학회지
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• 제18권5호
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• pp.1374-1381
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• 2004

The water extract of Dohongsamul-tang(DHSMT)has been traditionally used for treatment of ischemic heart in oriental medicine. However, little is known about the mechanism by which the water extract of DHSMT rescues cells from these damages. Therefore, this study was designed to evaluate the protective effects of DHSMT on zinc-mediated cytotoxicity in H9c2 cardiomyoblast cells. This study demonstrates that treatment of H9c2 cells with zinc caused a decrease in cell viability in a dose dependent manner and a chromatin condensation. Zinc induced the cleavage of poly(ADP-ribose) polymerase (PARP). In addition, zinc induced the decrease of Bcl-2, as well as increase of Bak expression and mitochondrial dysfunction. Zinc-induced H9c2 cell death was remarkably prevented by the pretreatment of DHSMT with consistent suppression of the cleavage of poly(ADP-ribose) polymerase (PARP), mitochondrial dysfunction and the expression of Bak and Bcl-2. Taken together, the results suggest that zinc induced severe cell death in H9c2 cardiomyoblast cells via intracellular GSH(reduced glutathione) depletion and the protective effects of DHSMT against oxidative injuries may be achieved through modulation of mitochondrial dysfunction and scavenging of ROS(reactive oxygen species).

• Biomolecules & Therapeutics
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• 제32권3호
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• pp.267-280
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• 2024

Apoptosis, programmed cell death pathway, is a vital physiological mechanism that ensures cellular homeostasis and overall cellular well-being. In the context of cancer, where evasion of apoptosis is a hallmark, the overexpression of anti-apoptotic proteins like Bcl2, Bcl-xL and Mcl-1 has been documented. Consequently, these proteins have emerged as promising targets for therapeutic interventions. The BCL-2 protein family is central to apoptosis and plays a significant importance in determining cellular fate serving as a critical determinant in this biological process. This review offers a comprehensive exploration of the BCL-2 protein family, emphasizing its dual nature. Specifically, certain members of this family promote cell survival (known as anti-apoptotic proteins), while others are involved in facilitating cell death (referred to as pro-apoptotic and BH3-only proteins). The potential of directly targeting these proteins is examined, particularly due to their involvement in conferring resistance to traditional cancer therapies. The effectiveness of such targeting strategies is also discussed, considering the tumor's propensity for anti-apoptotic pathways. Furthermore, the review highlights emerging research on combination therapies, where BCL-2 inhibitors are used synergistically with other treatments to enhance therapeutic outcomes. By understanding and manipulating the BCL-2 family and its associated pathways, we open doors to innovative and more effective cancer treatments, offering hope for resistant and aggressive cases.

• 동의생리병리학회지
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• 제18권6호
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• pp.1661-1665
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• 2004

Herba Patriniae(HP) has been known to exert anti-tumoral activity in Korea. However, its molecular mechanism, of action is not understood. In this study, we found that HP induced apoptosis in androgen-dependent prostate cancer DU145 cells as evidenced by DNA fragmentation and chromatine condensation in hoechst dye staining. Our data demonstrated that HP-induced apoptotic cell death was accompanied by activation of caspase-3 and cleavages of its substrates, poly(ADP-ribose) polymerase(PARP) in a time- and concentration-dependent manner. Taken together, these results suggest that HP induces the activation of caspase-3, degradation of PARP, and eventually leads to apoptotic cell death.

• 동의생리병리학회지
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• 제16권3호
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• pp.514-520
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• 2002

Paljinhangahm-dan is an Oriental herbal formulation for its ability to modulate cancer cell growth and survival. This research was performed to study the anti-cancer effects of Paljinhangahm-dan water extract(PHWE) in human pro myelocytic leukemia(HL-60) cells. After HL-60 cells were routinely cultured, tetrazolium-based colorimetric(MTT) assay was performed for cytotoxicity test. To explore the mechanism of cytotoxicity. I used several measures of apoptosis to determine whether this processes was involved in PHWE-induced cell death in HL-60 cells. In addition, the experiment was practised 1 H-NMR spectroscopy to examine molecular structure of PHWE. This study suggested that PHWE control cancer cell growth through of apoptosis with less cytotoxicity in normal cells.

• 동의생리병리학회지
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• 제22권3호
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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.

• 동의생리병리학회지
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• 제19권4호
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• pp.1050-1054
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• 2005

Recently, arsenic compounds were considered as novel agents for treatment of acute promyelocytic leukemia and malignant tumors. However, it showed severe toxicity effect on normal tissue at the same time. In this study, to investigate the possible molecular mechanism (s) of arsenic compounds as candidate of anti-cancer drugs, we compared the abilities of two arsenic compounds, tetraarsenic oxide $(AS_4O_6)$ and arsenic trioxide (diarsenic oxide, $As_2O_3$), to induce cell growth inhibition as well as apoptosis induction in A549 human non-small cell lung cancer cells. Both $As_4O_6\;and\;As_2O_3$ treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of G1 arrest of the cell cycle and apoptotic cell death. However, $As_4O_6$ induced growth inhibition and apoptosis in A549 cells at much lower concentrations than $As_2O_3.\;As_4O_6$ down-regulated the levels of anti-apoptotic Bcl-2 protein, however, the levels of Bax, a pro-apoptotic protein, were up-regulated in a dose-dependent manner. In conclusion, $As_4O_6$ might be a new arsenic compound which may induce apoptosis in A549 cells by modulation the Bcl-2 family and deserves further evaluation.

• 동의생리병리학회지
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• 제16권2호
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• pp.296-302
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• 2002

Bohyulmyunyuk-dan is an Oriental herbal formulation to enhance the general body conditions as well as immune response against both endogenous and exogenous harmful challenges. This study was designed to investigate the effect of Bohyulmyunyuk-dan on the cisplatin-induced toxicity of primary rat astrocytes and C6 glioma cells. After trestment of astrocytes and C6 glioma cells with cisplatin, MTT assay was carried out to measure cytotoxicity of brain cells. To explore the mechanism of cytotoxicity, astrocytes were treated with Bohyulmyunyuk-dan and followed by the addition of cisplatin. Then, the protective effects of Bohyulmyunyuk-dan were investigated in apoptosis signaling pathway. The results were obtained as follows ; Bohyulmyunyuk-dan protected the death of astrocytes by cisplatin, which decreased the viability of astrocytes and C6 glioma cells in a time- and dose-dependent manner. Bohyulmyunyuk-dan protected the apoptotic death of astrocytes from cisplatin induced cell apoptosis. Bohyulmyunyuk-dan inhitited the activation of caspase-3 and -9 protease in astrocytes by cisplatin. Bohyulmyunyuk-dan inhibited the deavage of PARP in astrocytes by cisplatin. According to above results, Bohyulmyunyuk-dan may prevent brain cells from cytotoxicity induced cell apoptosis induced by chemotherapeatic agents induding displatin.

• 동의생리병리학회지
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• 제23권3호
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• pp.581-589
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• 2009

The water extract of Dohongsamul-tang(DHSMT) has been traditionally used in treatment of ischemic heart and brain diseases in Oriental Medicine. However, little is known about the mechanism by which DHSMT protects C6 glial cells from glucose deprevation induced damages. Therefore, this study was designed to evaluate the protective effects of DHSMT on 2-deoxy-D-glucose induced autophagy of C6 glial cells. Autophagic phenotype is evaluated by fluorescence microscopy and flow cytometry with specific biological staining dyes, including monodansylcadaverine and acridine orange, as well as Western blot analysis with microtubule-associated protein 1 light chain 3(LC3) and Beclin-1. Treatment with 2-deoxy-D-glucose significantly resulted in a decrease of the viability of C6 glial cells and increase of the extracellular LDH release in a dose and time-dependent manner. However, pretreatment with DHSMT protected C6 glial cells from glucose deprivation with 2-deoxy-D-glucose. The author also observed the fact that autophagy phenotype occurred by 2-deoxy-D-glucose in C6 glial cells. Pretreatment with 3-MA, a pharmacological inhibitior of autophagy, abolished the formation of acidic vesicle organelle in C6 glial cells treated with 2-deoxy-D-glucose. However, pretreatment with DHSMT inhibited the formation of autophagic phenotypes, including formation of acidic vesicle organelle, and increase of the expression of LC-3 II Beclin-1 proteins in C6 glial cells treated with 2-deoxy-D-glucose. Taken together, these data suggest that DHSMT is able to protect C6 glial cells from glucose deprivation with marked inhibition of autophagy formation.

• 동의생리병리학회지
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• 제20권4호
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• pp.861-865
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• 2006

Takrisodokyeum (TRSDY) has been known to exert anti-tumoral activity in Korea. However, its molecular mechanism of action is not understood. In this study, we found that TRSDY induced apoptosis in androgen-independent prostate cancer DU145 cells as evidenced by DNA fragmentation and chromatine condensation in hoechst 33342 dye staining. Our data demonstrated that TRSDY-induced apoptotic cell death was accompanied by increases of PTEN and Par-4 in a time-dependent manner Taken together, these results suggest that TRSDY induce PTEN and Par-4 expression, and eventually lead to apoptotic cell death in androgen independent prostate cancer DU145 cells.

• 동의생리병리학회지
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• 제23권4호
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• pp.888-894
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• 2009

It has been reported that silibinin, a natural polyphenolic flavonoid, induces cell death in various cancer cell types. However, the underlying mechanisms by which silibinin induces apoptosis in human glioma cells are poorly understood. The present study was therefore undertaken to examine the effect of silibinin on glioma cell apoptosis and to determine its underlying mechanism in human glioma cells. Apoptosis was estimated by FACS analysis. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (${\Psi}m$) were measured using fluorescence dyes DCFH-DA and $DiOC_6$(3), respectively. Cytochrome c release from mitochondria and caspase-3 activation were estimated by Western blot analysis using specific antibodies. Exposure of cells to 30 mM silibinin induced apoptosis starting at 6 h, with increasing effects after 12-48h in a time-dependent manner. Silibinin caused ROS generation and disruption of ym, which were associated with the silibinin-induced apoptosis. The silibinin-induced ROS generation and disruption in ym were prevented by inhibitors of mitochondrial electron transport chain. The hydrogen peroxide scavenger catalase blocked ROS generation and apoptosis induced by silibinin. Silibinin induced cytochrome c release into cytosolic fraction and its effect was prevented by catalase and cyclosporine A. Silibinin treatment caused caspase-3 activation, which was inhibited by DVED-CHO and cyclosporine A. Pretreatment of caspase inhibitors also protected against the silibinin-induced apoptosis. These findings indicate that ROS generation plays a critical role in the initiation of the silibinin-induced apoptotic cascade by mediation of the mitochondrial apoptotic pathway including the disruption of ${\Psi}m$, cytochrome c release, and caspase-3 activation.