• Genomics & Informatics
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• v.4 no.2
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• pp.77-79
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• 2006

In order to identify novel proapoptotic genes, we screened approximately 1,000 hypothetical genes whose functions are completely unknown. After these genes were transiently expressed in HeLa cells, their nuclei images were captured using automated high-speed fluorescence microscope, through which the ratio of apoptotic nuclei was estimated. We selected genes that induce greater than 3-fold increase in apoptotic nuclei compared to that of the vector control. The candidate proapoptotic genes were sequenced and their effects on cell death were further confirmed by the additional assay, DNA fragmentation ELISA. Finally, we were able to identify 4 full-length hypo-thetical genes with proapoptotic activity.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3797-3803
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• 2016

Cervical cancer is the second most common malignancy in women worldwide and thus one of the leading causes of mortality in women. Lovastatin, a non polar, anticholesterol drug has previously been reported to exert antitumour activity in vitro. In the present study, lovastatin from Aspergillus terreus (KM017963) was purified by adsoprtion chromatography and evaluated for its anticancer and anti-oxidant properties with a human cervical cancer cell line (HeLa). Growth inhibitory and proapoptotic effects of purified lovastatin on HeLa cells were investigated by determining its influence on cell numbers, mitochondrial membrane potential (MMP), DNA fragmentation and antioxidant properties in terms of hydroxy radical scavenging effects as well as levels of total reduced glutathione. Cell cycle analysis by flow cytometry (propidium iodide staining) confirmed induction of apoptotic cell death and revealed cell cycle arrest in the G0/G1 phase. Results of the study give leads for the anticancer effects of lovastatin and its potential usefulness in the chemotherapy of cervical cancer.

• Molecules and Cells
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• v.23 no.2
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• pp.170-174
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• 2007

High-throughput subcellular imaging is a powerful tool for investigating the function of genes. In order to identify novel regulators of apoptosis we transiently transfected HeLa cells with 938 hypothetical genes of unknown function, and captured their nuclear images with an automated fluorescence microscope. We selected genes that induced greater than 3-fold increase in the percentage of apoptotic nuclei compared with vector-transfected cells. The full-length genes C10orf61, MGC 26717, and FLJ13855 were identified as candidate proapoptotic genes, and their apoptotic effects were confirmed by DNA fragmentation ELISAs and Western blotting for caspase-7 and PARP. We conclude that a subcellular image-based apoptotic screen is useful for identifying genes with proapoptotic activity.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.96-104
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• 2020

Objectives: Oleanolic acid, a minor element of ginsenosides, and its derivatives have been shown to have cytotoxicity against some tumor cells. The impact of cytotoxic effect of oleanolic acid 3-acetate on ovarian cancer SKOV3 cells and endometrial cancer HEC-1A cells were examined both in vivo and in vitro to explore the underlying mechanisms. Methods: Cytotoxic effects of oleanolic acid 3-acetate were assessed by cell viability, phosphatidylserine exposure on the cell surface, mitochondrial release of cytochrome C, nuclear translocation of apoptosis-inducing factor, depolarization of mitochondrial transmembrane potential (∆Ψ_m), and generation of reactive oxygen species (ROS). In vivo inhibition of tumor growth was also assessed with xenografts in immunocompromised mice. Results: Oleanolic acid 3-acetate exhibited potent cytotoxicity toward SKOV3 and HEC-1A cells by decreasing cell viability in a concentration-dependent manner. Importantly, oleanolic acid 3-acetate effectively suppressed the growth of SKOV3 cell tumor xenografts in immunocompromised mice. Furthermore, oleanolic acid 3-acetate induced apoptotic cell death as revealed by loss of ∆Ψ_m, release of cytochrome c, and nuclear translocation of apoptosis-inducing factor with a concomitant activation of many proapoptotic cellular components including poly(ADP-ribose) polymerase, Bcl-2, and caspases-8, caspase-3, and caspase-7. Oleanolic acid 3-acetate, however, caused a decrease in ROS production, suggesting the involvement of an ROS-independent pathway in oleanolic acid 3-acetate-induced apoptosis in SKOV3 and HEC-1A cells. Conclusion: These findings support the notion that oleanolic acid 3-acetate could be used as a potent anticancer supplementary agent against ovarian and endometrial cancer. Oleanolic acid 3-acetate exerts its proapoptotic effects through a rather unique molecular mechanism that involves an unconventional ROS-independent but mitochondria-mediated pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1502-1506
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• 2006

To investigate the inhibitory effects of Citaowan (CTW) on the growth and angiogenesis of breast cancer in vivo. Orthotopic breast cancer model was established by injection of MDA-MB-231 cells into mammary fat pad of nude mice. Seven weeks after injection, CTW was orally administered at dose of 50, 100 mg/mouse every day for 40 days. Body weight, tumor volume, tumor apoptosis, microvessel density and tumor proliferation were evaluated, after the mice were sacrificed. The body weight and tumor volume were not significantly changed in CTW group compared with the control group. Tumor apoptosis, proliferation and microvessel density were significantly reduced in CTW group (100 mg/mouse) compared with the control group. These data indicate that CTW has anti-angiogenic and proapoptotic effects on breast cancer.

• Journal of Microbiology and Biotechnology
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• v.18 no.10
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• pp.1655-1658
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• 2008

Cyanobacteria, blue-green algae, are a rich source of bioactive secondary metabolites with many potential applications. The ubiquitin-proteasome proteolytic system plays an important role in selective protein degradation and regulates cellular events including apoptosis. Cancer cells are more sensitive to the proapoptotic effects of proteasome inhibition than normal cells. Thus, proteasome inhibitors can be potential anticancer agents. Cyanobacteria have been shown to be a rich source of highly effective inhibitors of proteases. A proteasome inhibitor was screened from an extract of the culture of Scytonema hofmanni on the basis of its inhibitory activity, which led to the isolation of nostodione A with an $IC_{50}$ value of 50${\mu}M$. Its structure was determined by spectroscopic methods such as $^{1}H$-NMR and ESI-MS spectral analyses.

• 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.

• Toxicological Research
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• v.18 no.3
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• pp.275-283
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• 2002

Fungal metabolite, gliotoxin is an epipolythiodioxopiperazin (ETP) class and has various roles including immunomodulatory and apoptotic effects. This study was designed to evaluate the mechanism by which gliotoxin exerts the apoptosis on human promyelocytic leukemic HL-60 cells. Herein, we demonstrated that the gliotoxin decreased the cell viability in a time-dependent manner Gliotoxin-induced cell death was confirmed us apoptosis characterized by chromatin condensation and ladder-pattern fragmentation of genomic DNA. Gliotoxin increased the catalytic activities of caspase-3 and caspase-9. Activation of caspase-3 was further confirmed by degradation of procaspase-3 and poly(ADP-ribose) polymerase (PARP) by gliotoxin in HL-60 cells. Furthermore, gliotoxin induced the changes of mitochondrial transmembrane potential (MTP). Antioxidants, including GSH and NAC, markedly inhibited apoptosis with conistent suppression of enzymatic activity of caspase-3, caspase-9, and MTP loss in gliotoxin-treated cells. Taken together, we suggest that gliotoxin function as an oxidant and ploys proapoptotic roles in HL-60 cells via activation of intrinsic caspase cascades as well as mitochondrial dysfunction.

• Korean Journal of Pharmacognosy
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• v.39 no.1
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• pp.56-59
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• 2008

Ubiquitin-proteasome proteolytic system plays an important role in selective protein degradation and regulates cellular events including apoptosis. Cancer cells have been shown to be more sensitive to the proapoptotic effects of proteasome inhibition than normal cells. Thus, proteasome inhibitor can be potential anticancer agent. Since the MeOH extracts of psoraleae semen and processed psoraleae semen showed potent proteasome inhibition activity, the fractions of the extracts were evaluated on the activity to screen the proteasome inhibitors. The $CHCl_3$ fr. of the processed psoraleae semen showed the most potent activity, of which chemical investigation led to two coumarins, psoralen and isopsoralen. Their structures were determined by spectroscopic methods such as $^1H-NMR$ and EIMS spectra.

• Food Science and Biotechnology
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• v.18 no.2
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• pp.552-555
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• 2009

This study investigated the proapoptotic effect of ethanol extracts obtained from dandelion (Taraxacum officinale) flower on human ovarian cancer SK-OV-3 cells. Cells were treated with dandelion flowers ethanol extract (DFE) ranging from 1.5625 to $100{\mu}g/mL$ for 24 hr. Significant antiproliferative effects of DFE were first observed from at $6.25{\mu}g/mL$ (p<0.05), and this inhibition showed in a dose-dependent manner. When cells were treated with more than $6.25{\mu}g/mL$ DFE, cell-cycle analysis showed that DFE caused an increase in the percentage of sub-G0/G1 cells and arrested at the S and G2/M phase in a dose-dependent manner. Moreover, apoptosis induction by DFE involved p53 activation and bax upregulation as well as downregulation of bcl-2. Our findings indicate that DFE resulted in apoptotic cell death, suggesting that DFE possesses potential anticancer properties.