• International Journal of Oral Biology
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• v.32 no.3
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• pp.113-118
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• 2007

Treatment of oral cancers with chemotherapeutic agents become evaluated as an effective method to reduce cancer cell proliferation. Anti-proliferative and anti-oral cancer activities of momordin I on oral cancer cells were evaluated in this study. Momordin I was originally purified from a natural product, Ampelopsis radix and showed the antiproliferative activity against oral carcinoma, KB cells. Obtained $IC_{50}$ value was approximately $10.4{\mu}g/ml$. Time-and dose-dependent chromosomal DNA fragmentations were observed in momordin I-treated KB cells. Flow cytometry analysis showed time-dependent apoptotic cell appearance after treatment of momordin I. Approximately 18.6% apoptotic cells were observed at 72 hours after $20{\mu}g/ml$ of momordin I treatment. These observation were consistent with the results obtained in DNA fragmentation analysis. These data suggest that momordin I has anti-proliferative effect and induces cell death in KB cells through apoptosis.

• Journal of Korean Neurosurgical Society
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• v.40 no.1
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• pp.1-5
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• 2006

Objective : Survivin is an inhibitor of apoptosis protein[IAP], which inhibits apoptosis through a pathway distinct from the Bcl-2 family members. Overexpression of survivin and Bcl-2 have been commonly reported in human neoplasms. The authors investigate whether there is a synergistic effect on the anti-apoptosis rate of primary brain tumors "in situ" based on the co-expression of survivin and Bcl-2. Methods : One hundred and two brain tumor patients who had been resected were included in this study. Survivin tin and Bcl-2 were detected by Western blotting analysis, while apoptosis was examined by DNA fragmentation analysis. An anti-apoptotic rate was assessed in these brain tumor samples based on the expression of survivin and Bcl-2 or co-expression of both. Results : Survivin and Bcl-2 were expressed in 57[55.9%] and 53[52.0%] of 102 brain tumor samples studied respectively, and co-expressed in 31[30.4%]. The percentage of astrocytic and meningeal tumors expressing survivin was significantly correlated with histological grades; however, Bcl-2 was not correlated [p=0.106]. The anti-apoptotic rate in primary brain tumors with survivin, Bcl-2, and both was detected in 49[86.0%] of 57 samples, 42[79.9%] of 53 samples, and 27[87.1%] of 31 samples, respectively. Their difference in the frequency of anti-apoptosis was not significant. Conclusion : Survivin or Bcl-2 is involved in the anti-apoptosis. However, it suggests that co-expression of survivin and Bcl-2, together, have no synergistic effect on the anti-apoptotic properties of the primary brain tumors.

• Clinical and Experimental Pediatrics
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• v.52 no.6
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• pp.696-700
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• 2009

Purpose : We screened more than 350 compounds with an endoperoxide ring structure in search of an anti-leukemic drug and found that compound 127 (c-127) could induce significant cytotoxicity in HL-60 cells. In this study, we investigated the molecular mechanisms of compound 127-induced antitumor activity on HL-60 cells. Methods : HL-60 cells were cultured in Rosewell Park Memorial Institute 1640 and cell viability was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], a tetrazole assay. Apoptosis was assessed by a DNA fragmentation test. Apoptotic machineries were determined by Western blot analysis. Results : C-127 could induce a cytotoxic effect at 24 h and apoptosis at 6 h, which was demonstrated with MTT assay and DNA fragmentation test, respectively. The apoptotic effect of this drug was caused by the activation of the intracellular caspase-8,3 activation, the cleavage of pro-apoptotic Bid, and the increase of c-Jun expression accompanied with JNK (Jun N-terminal kinases) phosphorylation. On the contrary, it increased the expression of anti-apoptotic Bcl-2 levels, leading to the induction of the induction of anti-apoptotic effect. Taken together, the present study demonstrated that c-127 was a potent inducer of cytotoxicity on HL-60 cells through apoptotic mechanisms, which included the activation of caspase family, the regulation of Bcl-2 family, and the activation of JNK signaling pathway. Conclusion : Our results suggest that c-127 has a strong antitumor activity through the regulation of various apoptotic machineries on HL-60 cells. The compound may be utilized as an effective and potentially therapeutic drug in leukemia.

• Journal of Acupuncture Research
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• v.30 no.1
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• pp.57-70
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• 2013

This study was to investigated the effects of the bee venom on inhibition of cell growth via upregulation of death receptor expression in the A549 human lung cancer cells. Bee venom(1-5 ${\mu}g$/ml) inhibited the growth of A549 lung cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of TNFR1, Fas, death receptors(DR) 3, 4 and 6 was increased in the cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, -9 and Bax was concomitantly increased, but the expression of Bcl-2, NF-${\kappa}B$ were inhibited by treatment with bee venom in A549 cells. Moreover, deletion of DR3, DR4 by small interfering RNA significantly reversed bee venom-induced cell growth inhibitory effect, whereas Apo3L strengthened anti-proliferative effect of bee venom through enhancement of DR3 expression. These results suggest that bee venom should exert anti-tumor effect through induction of apoptotic cell death in lung cancer cells via enhancement of death receptor expression, and that bee venom could be a promising agent for preventing and treating lung cancer.

• Biomedical Science Letters
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• v.22 no.4
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• pp.211-214
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• 2016

House dust mite is an essential allergen in the pathogenesis of allergic diseases. Abnormal regulation of neutrophil apoptosis is an important pathogenic process in allergic diseases. In the present study, we investigated the effects of house dust mites on spontaneous apoptosis of neutrophils and its associated mechanisms. Extract of Dermatophagoides pteronissinus (DP) inhibited neutrophil apoptosis in a time-dependent manner. Cycloheximide (CHX), an inhibitor of translation, increased apoptosis of DP-treated neutrophils as well as control cells. The pro-apoptotic effect of CHX was blocked by DP in neutrophils. In addition, DP increased the phosphorylation of Bad in a time-dependent manner, indicating that it exerted an inhibitory effect on the function of Bad. These results suggest that DP has anti-apoptotic effects of neutrophils and may regulate protein synthesis and activation of Bad. Moreover, these findings may shed light on elucidation of allergy pathogenesis due to house dust mites.

• Proceedings of the Korean Environmental Sciences Society Conference
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• 2020.10a
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• pp.219-219
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• 2020

Kaempferol (3,4',5,7-tetrahydroxyflavone), a flavonoid found in beans, broccoli, garlic, etc., has been used in natural medicine as an anti-inflammatory and antioxidant. This experiment was carried out to evaluate the anti-apoptotic effect of kaempferol in 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated Normal Human Dermal Fibroblast (NHDF). Kaempferol inhibited the production of intracellular Reactive Oxygen Species (ROS) induced by TPA in NHDF. Kaempferol significantly blocks the phosphorylation of extracellular signal-regulated kinase responsible for the activation of nuclear factor-kappa B. In addition, kaempferol significantly attenuated the expression of Bax and cleaved caspase-3 as regulated by the phosphorylation of nuclear factor-kappa B during its blockage of TPA-induced apoptotic cell death. These findings suggest that kaempferol protects the apoptotic signaling pathway induced by TPA through modulating intracellular ROS in NHDF.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.1
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• pp.51-55
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• 2004

Sopungsungi-won has been used as a traditional medicine for diabetes and it has been proved to be a potential remedy for type 2 diabetes mellitus. We previously reported that water extract of Sopungsungi-won exhibits anti-diabetic effects both in vivo and in vitro experiments. In the present study, we have chosen to examined anti-apoptotic effect of Rheum undulatum, which is the main component of Sopungsungi-won, on pancreatic ${\beta}-cells$, HIT-T15, against hydrogen peroxide $(H_2O_2)$. oxidative stress. To investigate the anti-apoptotic effect of Rheum undulatum water extract (RUWE) against $H_2O_2-induced$ apoptosis in pancreatic ${\beta}-cell$ line of hamster, HIT-T15, MTT assay, DAPI staining, TUNEL assay, RT-PCR and caspase-3 enzyme assay were performed. The morphological analysis demonstrated that cells treated with $H_2O_2$ exhibited classical apoptotic features, while such changes was reduced in cells pre-treated with RUWE. In addition, RUWE pre-treated cells prior to $H_2O_2$ treatment induced increase of levels of bcl-2 expression and decrease of caspase-3 enzyme activity compared to cells treated with $H_2O_2$ only. These results provide the possibility of usage of RU in patients with progressively deteriorated diabetes.

• IMMUNE NETWORK
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• v.5 no.2
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• pp.110-116
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• 2005

Background: As an attempt to develop a strategy to improve the protective immune response to GM-CSF-secreting CT26 (GM-CSF/CT26) tumor vaccine, we have investigated whether the apoptogenic treatment of GM-CSF/CT26 prior to vaccination enhances the induction of anti-tumor immune response in mouse model. Methods: A carcinogeninduced mouse colorectal tumor, CT26 was transfected with GM-CSF gene using a retroviral vector to generate GM-CSF-secreting CT26 (CT26/GM-CSF). The CT26/GM-CSF was treated with ${\gamma}$-irradiation or mitomycin C to induce apoptosis and vaccinated into BALB/c mice. After 7 days, the mice were injected with a lethal dose of challenge live CT26 cells to examine the protective effect of tumor vaccination in vivo. Results: Although both apoptotic and necrotic CT26/GM-CSF vaccines were able to enhance anti-tumor immune response, apoptotic CT26/GM-CSF induced by pretreatment with ${\gamma}$-irradiation (50,000 rads) was the most potent in generating the anti-tumor immunity, and thus 100% of mice vaccinated with the apoptotic cells remained tumor free for more than 60 days after tumor challenge. Conclusion: Apoptogenic pretreatment of GM-CSF-secreting CT26 tumor vaccine by ${\gamma}$-irradiation (50,000 rads) resulted in a significant enhancement in inducing the protective anti-tumor immunity. A rapid induction of apoptosis of CT26/GM-CSF tumor vaccine at the vaccine site might be critical for the enhancement in anti-tumor immune response to tumor vaccine.

• 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.

• Journal of Microbiology and Biotechnology
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• v.25 no.7
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• pp.1036-1046
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• 2015

Extracts from Asian medicinal herbs are known to be successful therapeutic agents against cancer. In this study, the effects of three types of herbal extracts on anti-tumor growth were examined. Among the three types of herbal extracts, H9 showed stronger anti-tumor growth effects than H5 and H11 in vivo. To find the molecular mechanism by which H9 inhibited the proliferation of breast cancer cell lines, the levels of apoptotic markers were examined. Proapoptotic markers, including cleaved PARP and cleaved caspases 3 and 9, were increased, whereas the anti-apoptotic marker Bcl-2 was decreased by H9 treatment. Next, the combined effect of H9 with the chemotherapeutic drugs doxorubicin/cyclophosphamide (AC) on tumor growth was examined using 4T1-tumor-bearing mice. The combined treatment of H9 with AC did not show additive or synergetic anti-tumor growth effects. However, when tumor-bearing mice were co-treated with H9 and the targeted anti-tumor drug trastuzumab, a delay in tumor growth was observed. The combined treatment of H9 and trastuzumab caused an increase of natural killer (NK) cells and a decrease of myeloid-derived suppressor cells (MDSC). Taken together, H9 induces the apoptotic death of tumor cells while increasing anti-tumor immune activity through the enhancement of NK activity and diminishment of MDSC.