• BMB Reports
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• v.36 no.3
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• pp.269-274
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• 2003

In the fight against cancer, novel chemotherapeutic agents are constantly being sought to complement existing drugs. Various studies have presented evidence that the apoptosis that is induced by these anticancer agents is implicated in tumor regression, and Bcl-2 family genes play a part in apoptosis following treatment with various stimuli. Here, we present data that a styrylpyrone derivative (SPD) that is extracted from the plant Goniothalamus sp. showed cytotoxic effects on the human breast cancer cell line MCF-7. SPD significantly increased apoptosis in MCF-7 cells, as visualized by phase contrast microscopy and evaluated by the Tdt-mediated dUTP nick end-labeling assay and nuclear morphology. Western blotting and immunostaining revealed up-regulation of the proapoptotic Bax protein expression. SPD, however, did not affect the expression of the anti-apoptotic protein, Bcl-2. These results, therefore, suggest SPD as a potent cytotoxic agent on MCF-7 cells by inducing apoptosis through the modulation of Bax levels.

• BMB Reports
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• v.48 no.2
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• pp.81-90
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• 2015

p73 is a structural and functional homologue of the p53 tumor suppressor protein. Like p53, p73 induces apoptosis and cell cycle arrest and transactivates p53-responsive genes, conferring its tumor suppressive activity. In addition, p73 has unique roles in neuronal development and differentiation. The importance of p73-induced apoptosis lies in its capability to substitute the pro-apoptotic activity of p53 in various human cancer cells in which p53 is mutated or inactive. Despite the great importance of p73-induced apoptosis in cancer therapy, little is known about the molecular basis of p73-induced apoptosis. In this review, we discuss the p73 structures reported to date, detailed structural comparisons between p73 and p53, and current understanding of the transcription-dependent and -independent mechanisms of p73-induced apoptosis.

• Journal of Microbiology and Biotechnology
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• v.19 no.8
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• pp.787-791
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• 2009

In the course of screening for substances that inhibit etoposide (10 ${\mu}g$/ml)-induced apoptosis in human leukemia U937 cells, fungal strain F000120, which exhibits potent inhibitory activity, was selected. The active compound was purified from an ethyl acetate extract of the microorganism by Sep-pak $C_{18}$ column chromatography and HPLC, and was identified as heptelidic acid (koningic acid) by spectroscopic methods. This compound inhibited caspase-3 induction in U937 cells with an $IC_{50}$ value of 40 ${\mu}M$ after 8 h of etoposide treatment. Fluorescent dye staining with acridine orange and ethidium bromide showed that heptelidic acid inhibited apoptosis. Furthermore, it was found that DNA fragmentation and caspase-3 activation, the biological hallmarks of apoptosis, were inhibited by the compound in a dose-dependent manner, suggesting that heptelidic acid inhibits etoposide-induced apoptosis via downregulation of caspases.

• Proceedings of the KSAR Conference
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• 2002.06a
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• pp.4-4
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• 2002

Male germ cell apoptosis has been extensively explored in rodent. In contrast, very little is known about their susceptibility to apoptosis stimuli of developing germ cell stages at the time when germ cell depletion after busulfan treatment occurs. Furthermore, it is still unanswered how spermatogonial stem cells are resistant to busulfan treatment. Spontaneous apoptosis of germ cells was observed in the testis of adult mice and experimentally induced busulfan treated mice increased this apoptosis to such an extent that there was a decrease in the weight of the testis. (omitted)

• BMB Reports
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• v.41 no.1
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• pp.11-22
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• 2008

Apoptosis (programmed cell death) is a cellular self-destruction mechanism that is essential for a variety of biological events, such as developmental sculpturing, tissue homeostasis, and the removal of unwanted cells. Mitochondria play a crucial role in regulating cell death. $Ca^{2+}$ has long been recognized as a participant in apoptotic pathways. Mitochondria are known to modulate and synchronize $Ca^{2+}$ signaling. Massive accumulation of $Ca^{2+}$ in the mitochondria leads to apoptosis. The $Ca^{2+}$ dynamics of ER and mitochondria appear to be modulated by the Bcl-2 family proteins, key factors involved in apoptosis. The number and morphology of mitochondria are precisely controlled through mitochondrial fusion and fission process by numerous mitochondria-shaping proteins. Mitochondrial fission accompanies apoptotic cell death and appears to be important for progression of the apoptotic pathway. Here, we highlight and discuss the role of mitochondrial calcium handling and mitochondrial fusion and fission machinery in apoptosis.

• Toxicological Research
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• v.32 no.4
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• pp.345-351
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• 2016

Propolis is a resinous material collected by honeybees from several plant sources. This research aimed at showing its protective effect against UVA-induced apoptosis of human keratinocyte HaCaT cells. Using Hoechst staining, it was demonstrated that propolis (5 and $10{\mu}g/mL$) significantly inhibited the apoptosis of HaCaT cells induced by UVA-irradiation. Propolis also showed the protective effect against loss of mitochondrial membrane potential induced by UVA-irradiaiton in HaCaT cells. Propolis also inhibited the expression of activated caspase-3 induced by UVA-irradiation. To investigate the role of ROS in UVA-induced apoptosis and protection by propolis, the generation of ROS was determined in cells. The results showed that the generation of ROS was markedly reduced in cells pretreated with propolis. Consequently, propolis protected human keratinocyte HaCaT cells against UVA-induced apoptosis, which might be related to the reduction of ROS generation by UVA-irradiation.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.190-197
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• 2004

Apoptosis plays a role in the pathophysiology of many kinds of diseases and in the response of treatment. Compared to the necrosis, the apoptosis is a genetically controlled and energy-dependent process which removes the unwanted cells from the body; programmed cell death or cell suicide. During the apoptosis, phosphatidylserine is expressed in the cytoplasmic outer membrane in the early phase. Annexin V, an endogenous human protein (MW=35 kD), has an affinity of about $10^{-9}\;M$ for the phosphatidylserine exposed on the outer membrane of apoptotic cells. Annexin V can be radiolabeled with $^{99m}Tc$ by HYNIC or EC chelators, which can be used as an radiotracer for the in vivo imaging of apoptosis. In this article, we reviewed the apoptosis, radiolabeling of annexin V, and the experimental and clinical data using annexin V imaging.

• Biomedical Science Letters
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• v.18 no.4
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• pp.420-427
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• 2012

Sprague-Dawley (SD) rats were orally administered with NG-nitro-L-arginine methyl ester (L-NAME), which inhibits or blocks the production of nitric oxide from L-arginine in vascular endothelial cells and vessel tissue. We examined the effects of nitric oxide on some physiological changes such as blood pressure and heart rate, and confirms the apoptosis induced by the suppressed nitric oxide activity in the kidney. This study was performed to investigate correlation between the activities of nitric oxide and apoptosis by immunohistochemical changes of apoptotic control proteins with regulated chronic inhibition of nitric oxide. In the kidney from L-NAME-treated group, immunohistochemical reaction to the antigens of apoptosis inhibiting proteins such as bcl-2 and bcl-xL, exhibited a time-dependent reduction. The expression of apoptosis-inhibiting proteins such as bax and p53 increased expression in proportion to the duration of treatment. The most sensitive apoptosis regulating proteins to L-NAME were p53 in stimulation and bcl-2 in inhibition, respectively.

• Toxicological Research
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• v.22 no.4
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• pp.329-332
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• 2006

Ethanolic extract of Aloe vera (Aloe barbadensis Miller) was examined for the cellular toxicity on HepG2 human hepatocellular carcinoma cells. Treatment with Aloe vera extract resulted in DNA fragmentation but not LDH release, suggesting an apoptosis instead of necrosis. Aloe vera induced cytotoxicity was mediated by decrease in ATP levels, whereas GSH depletion, increase in intracellular $Ca^{2+}$, or activation of caspase-3/7 could not be observed with statistical significance. No activation of caspase-3/7 suggests the possibility of caspase-independent apoptosis. Taken together, our results show that Aloe vera extract induce HepG2 apoptosis by ATP depletion-related impairment of mitochondria, which is caspase-independent.

• BMB Reports
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• v.38 no.3
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• pp.314-319
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• 2005

Adenosine, as a ubiquitous metabolite, mediates many physiological functions via activation of plasma membrane receptors. Mechanisms of most of its physiological roles have been studied extensively, but research on adenosine-induced apoptosis (AIA) has only started recently. In this study we demonstrate that adenosine dose-dependently triggered apoptosis of cultured baby hamster kidney (BHK) cells. Adenosine-induced apoptotic cell death was characterized by DNA laddering, changes in nuclear chromatin morphology and phosphatidylserine staining. Apoptosis was also quantified by flow cytometry. Results suggest the involvement of adenosine $A_1$ and $A_3$ receptors as well as equilibrative nucleoside transporters in apoptosis induced by adenosine. These results indicate a receptor-transporter co-signaling mechanism in AIA in BHK cells. The involvement of $A_1$ and $A_3$ receptors also implies a possible apoptotic pathway mediated by G protein-coupled receptors.