• 셀메드
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• 제2권3호
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• pp.26.1-26.5
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• 2012

Adverse side-effects and lack of scientific validation of some chemotherapeutic agents prevent the use of many traditional medicines claimed to have anti-cancer effects. Ethanolic extract of Conium maculatum has long been used in traditional and alternative systems of medicine including homeopathy for the treatment of glandular enlargements, cancerous tumours or hard lumps of testicles, prostate, ovaries, breasts and/ or uterus, particularly in the breast. However, if and how it acts still remains scientifically unknown. This study aims to test if Conium extract (CE), used as mother tincture of Conium in homeopathy, has demonstrable anti-cancer potentials without having much cytotoxicity in normal cells. Cytotoxicity of the drug was tested by conducting MTT assay on both normal (peripheral blood mononuclear cells) and HeLa cells. We also evaluated DNA fragmentation and DNA damage by DAPI and diphenylamine assay. The LDH activity assay was done to evaluate the percentages of apoptosis and necrosis. ROS accumulation also was evaluated to pin-point the actual events of apoptosis. Administration of drug clearly demonstrated its anti-cancer potentials as evidenced by the DNA damage analysis. The ROS activity also increased in case of the CE treated cells. LDH data revealed that the mode of cell death was mainly apoptotic and not necrotic. CE appears to induce apoptosis of cancer cells through ROS mediated pathway, and has negligible cytotoxicity against normal cells.

• Molecules and Cells
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• 제37권2호
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• pp.178-186
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• 2014

Differential transcription of the clusterin (CLU) gene yields two CLU isoforms, a nuclear form (nCLU) and a secretory form (sCLU), which play crucial roles in prostate tumorigenesis. Pro-apoptotic nCLU and anti-apoptotic sCLU have opposite effects and are differentially expressed in normal and cancer cells; however, their regulatory mechanisms at the transcriptional level are not yet known. Here, we examined the transcriptional regulation of nCLU in response to hypoxia. We identified three putative hypoxia response elements (HREs) in the human CLU promoter between positions -806 and +51 bp. Using a luciferase reporter, electrophoretic gel mobility shift, and chromatin immunoprecipitation assays, we further showed that hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) bound directly to these sites and activated transcription. Exposure to the hypoxia-mimetic compound $CoCl_2$, incubation under 1% $O_2$ conditions, or overexpression of HIF-$1{\alpha}$ enhanced nCLU expression and induced apoptosis in human prostate cancer PC3M cells. However, LNCaP prostate cancer cells were resistant to hypoxia-induced cell death. Methylation-specific PCR analysis revealed that the CLU promoter in PC3M cells was not methylated; in contrast, the CLU promoter in LNCap cells was methylated. Co-treatment of LNCaP cells with $CoCl_2$ and a demethylating agent promoted apoptotic cell death through the induction of nCLU. We conclude that nCLU expression is regulated by direct binding of HIF-$1{\alpha}$ to HRE sites and is epigenetically controlled by methylation of its promoter region.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.132-132
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• 2002

• 대한약침학회지
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• 제18권3호
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• pp.32-41
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• 2015

Objectives: Condurango (Gonolobus condurango) extract is used by complementary and alternative medicine (CAM) practitioners as a traditional medicine, including homeopathy, mainly for the treatment of syphilis. Condurango bark extract is also known to reduce tumor volume, but the underlying molecular mechanisms still remain unclear. Methods: Using a cervical cancer cell line (HeLa) as our model, the molecular events behind condurango extract's (CE's) anticancer effect were investigated by using flow cytometry, immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR). Other included cell types were prostate cancer cells (PC3), transformed liver cells (WRL-68), and peripheral blood mononuclear cells (PBMCs). Results: Condurango extract (CE) was found to be cytotoxic against target cells, and this was significantly deactivated in the presence of N-acetyl cysteine (NAC), a scavenger of reactive oxygen species (ROS), suggesting that its action could be mediated through ROS generation. CE caused an increase in the HeLa cell population containing deoxyribonucleic acid (DNA) damage at the G zero/Growth 1 (G0/G1) stage. Further, CE increased the tumor necrosis factor alpha ($TNF-{\alpha}$) and the fas receptor (FasR) levels both at the ribonucleic acid (RNA) and the protein levels, indicating that CE might have a cytotoxic mechanism of action. CE also triggered a sharp decrease in the expression of nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) both at the RNA and the protein levels, a possible route to attenuation of B-cell lymphoma 2 (Bcl-2), and caused an opening of the mitochondrial membrane's permeability transition (MPT) pores, thus enhancing caspase activities. Conclusion: Overall, our results suggest possible pathways for CE mediated cytotoxicity in model cancer cells.

• 한국자원식물학회지
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• 제31권3호
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• pp.218-227
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• 2018

In this study, we investigated the effect of the extracts from Vaccinium oldhamii on cell proliferation and the regulatory mechanisms of cyclin D1 protein level in human cancer cells. The branch extracts from Vaccinium oldhamii (VOB) showed higher inhibitor effect against the cell growth than leave extracts (VOL) and fruit extracts (VOF) in human colorectal cancer, breast cancer, prostate cancer, non-small lung cancer, pancreatic cancer and liver cancer cells. In addition, VOB decreased cyclin D1 level at both protein and mRNA level. MG132 treatment attenuated VOB-mediated cyclin D1 downregulation. A point mutation of threonine-286 to alanine attenuated cyclin D1 degradation by VOB. In addition, the inhibition of nuclear export by leptomycin B (LMB) attenuated cyclin D1 degradation by VOB. But, the treatment of PD98059 (ERK1/2 inhibitor), SB203580 (p38 inhibitor), SP600125 (JNK inhibitor), LiCl ($GSK3{\beta}$ inhibitor), LY294002 (PI3K inhibitor) or BAY 11-7082 ($I{\kappa}K$ inhibitor) did not affect VOB-induced cyclin D1 degradation. In conclusion, VOB induced cyclin D1 degradation through redistribution of cyclin D1 from the nucleus to cytoplasm via T286 phosphorylation of cyclin D1, which resulted in the inhibition of cancer cell proliferation.

• 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.

• Parasites, Hosts and Diseases
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• 제54권2호
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• pp.123-132
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• 2016

Trichomonas vaginalis causes the most prevalent sexually transmitted infection worldwide. Trichomonads have been detected in prostatic tissues from prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. Chronic prostatic inflammation is known as a risk factor for prostate enlargement, benign prostatic hyperplasia symptoms, and acute urinary retention. Our aim was to investigate whether T. vaginalis could induce inflammatory responses in cells of a benign prostatic hyperplasia epithelial cell line (BPH-1). When BPH-1 cells were infected with T. vaginalis, the protein and mRNA of inflammatory cytokines, such as CXCL8, CCL2, IL-$1{\beta}$, and IL-6, were increased. The activities of TLR4, ROS, MAPK, JAK2/STAT3, and NF-${\kappa}B$ were also increased, whereas inhibitors of ROS, MAPK, PI3K, NF-${\kappa}B$, and anti-TLR4 antibody decreased the production of the 4 cytokines although the extent of inhibition differed. However, a JAK2 inhibitor inhibited only IL-6 production. Culture supernatants of the BPH-1 cells that had been incubated with live T. vaginalis (trichomonad-conditioned medium, TCM) contained the 4 cytokines and induced the migration of human monocytes (THP-1 cells) and mast cells (HMC-1 cells). TCM conditioned by BPH-1 cells pretreated with NF-${\kappa}B$ inhibitor showed decreased levels of cytokines and induced less migration. Therefore, it is suggested that these cytokines are involved in migration of inflammatory cells. These results suggest that T. vaginalis infection of BPH patients may cause inflammation, which may induce lower urinary tract symptoms (LUTS).

• BMB Reports
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• 제41권10호
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• pp.722-727
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• 2008

The present study compared the proteomic characteristics of a low passage number (L-33) and high passage number (H-81) LNCaP cell clone. Marked differences in protein expression were noted in the response of L-33 and H-81 cells to androgens. To investigate if regulation of these proteins was androgen-dependent, expression of the androgen receptor was silenced via small interfering RNA. Consistent with the proteomic data, abrogation of androgen receptor production in H-81 cells resulted in the reversed expression level into L-33 cells compared with non-treated H-81 LNCaP cells. The results clarify the progression into an androgen-independent phenotype.

• Molecules and Cells
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• 제43권2호
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• pp.126-138
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• 2020

The transcription factor RUNX1 first came to prominence due to its involvement in the t(8;21) translocation in acute myeloid leukemia (AML). Since this discovery, RUNX1 has been shown to play important roles not only in leukemia but also in the ontogeny of the normal hematopoietic system. Although it is currently still challenging to fully assess the different parameters regulating RUNX1 dosage, it has become clear that the dose of RUNX1 can greatly affect both leukemia and normal hematopoietic development. It is also becoming evident that varying levels of RUNX1 expression can be used as markers of tumor progression not only in the hematopoietic system, but also in non-hematopoietic cancers. Here, we provide an overview of the current knowledge of the effects of RUNX1 dosage in normal development of both hematopoietic and epithelial tissues and their associated cancers.

• Archives of Pharmacal Research
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• 제17권2호
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• pp.100-103
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• 1994

The limonoid compound (28-deacetyl sendanin0 isolated from the fruit of Melia toosendan SIEB. et ZUCC. was evaluated on anticancer activity. According to a standard in vitro cytotoxicity assy, eight human cancer cell lines and SRB assay were introduced for present evaluation. As a positive standard, adriamycin was tested in parallel. The cell lines were originated from six different organs. In view of dose-response profiles to 28-deacetyl sendanin, the most sensitive cells were SF-539 and PC-3 which were derived from CNS and prostate, respecitively. In contrast, all the cell lines responded similarly to adriamycin to give rise to nearly indentical six cell lines were more sensitive to 28-deacetyl sendanin and two were more resistant. As a result, 28-deacetyl sendanin had more senstive and selective inhibitory effects on in vitro growth of human cancer cell lines in a comparison with adriamycin.